Multiple Sclerosis

With chronic pain common among people with multiple sclerosis (MS), approximately 20% of patients report opioid use - despite warnings that the drugs are generally not recommended for the management of chronic pain and ongoing concerns of addiction, new research shows.

“This high level of opioid use supports that better pain management treatment options, including nonpharmacological options, are needed for people with MS and pain,” wrote the authors of the study, which was presented at ACTRIMS Forum 2021, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Previous research has shown that more than 50% of people with MS report chronic pain that is serious enough to interfere with daily activities, employment, and quality of life. Many with MS report that pain is one of their worst symptoms, the authors noted.

With surprisingly few studies evaluating opioid use in the MS population, Cinda L. Hugos, PT, associate professor of neurology with the VA Portland Health Care System and the department of neurology, Oregon Health and Science University, Portland, and colleagues investigated the issue in a sample of patients participating in a U.S. multisite MS fatigue management trial conducted between 2013 and 2014.

Of the 281 participants with MS in the study, 58 patients (20.6%) reported using prescription opioids. Among them, most – 44 (76%) – reported regular daily use, 10 (17%) reported using the drugs only as needed, 3 (5%) reported only short-term use, including after recent injury or dental surgery, and 1 provided incomplete information.

Those who reported opioid use had significantly worse fatigue scores on the Modified Fatigue Impact Scale (P = .015) and worse pain scores (P < .0001).

There were no significant differences in terms of age (mean age, 53 years), gender (69% were female), or race (in both groups, about 76% were White). No significant differences were seen in disability or depression scores in the opioid users versus nonusers.

“In this sample of people with multiple sclerosis who self-reported fatigue and volunteered to join an MS fatigue management research study, more than one in five reported using prescription opioids and nearly one in six used opioids daily,” the authors wrote. “Opioid users had more pain and fatigue than nonusers.”

Commenting on the study, Jeffrey Cohen, MD, president of ACTRIMS, said that the findings are consistent with his observations that “in the general population, opioids often are used to treat chronic pain in people with MS.”

But they’re not getting the drugs from his clinic. “We do not prescribe opioids in our clinic, referring such patients to a chronic pain program,” Dr. Cohen said. “However, there clearly is need for better treatment options.”

A previous study on opioid use by people with MS, published in 2015, found even higher rates – 42% reported having ever used opioids, and 38% reported currently using opioids.

Although reports of opioid use by patients with MS have been lacking, more has been published on the emerging use of cannabis-related products. One recent study showed that nearly half of people with MS reported using a cannabis-based therapy for nerve-based pain and sleep disturbances.

Although cannabis is considered safer than opioids, the authors noted that it has its own significant drawback – a “paucity of provider guidance.”

“The range of perceived benefits and potential differential effects of THC and cannabinoid highlight the need for personalized, evidence-based guidelines regarding cannabinoid use,” they wrote.
 

Stretching program for spasticity shows benefits

With spasticity representing a key contributor to MS pain and affecting more than 80% of people with MS, Ms. Hugos and colleagues are developing an alternative to medication – a nonpharmacologic stretching regimen called Spasticity: Take Control” (STC).

Based on evidence-based strategies for the treatment of spasticity in MS, the program involves exercises with daily routines of 15-20 minutes over 6 months.

In a pilot study of 66 patients, also presented at the ACTRIMS meeting, the investigators reported that the program showed significant reductions in pain severity and interference, measured with the Brief Pain Inventory–Short Form, compared with a control consisting of range of motion instruction over 6 months.

The study also offered insights on the specific areas of pain. Among those who reported chronic pain (42% in the STC group and 63.3% in the range-of-motion group), the pain was most frequently reported in the lower back (74.3%), legs (68.6%), or lower back and legs (88.6%).

Ms. Hugos noted that the findings suggest a potentially important nonpharmacologic alternative to spasticity-related pain in MS.

“Stretching is the cornerstone treatment for spasticity from all causes, but there is very little information on stretching exercises in MS or any other conditions,” Ms. Hugos said. “[Our] pilot study is the first and only study using a standardized, daily stretching exercise program to treat MS spasticity,” she said.

“A fully powered study is needed to better understand the impact of different types of exercise on pain severity and interference in multiple sclerosis,” she noted.

Ms. Hugos has received consulting fees from Greenwich Biosciences, Evidera, and Techspert.io. Dr. Cohen has received personal compensation for consulting for Adamas, Atara, Bristol-Myers Squibb, Convelo, MedDay, and Mylan.

A version of this article first appeared on Medscape.com.

With chronic pain common among people with multiple sclerosis (MS), approximately 20% of patients report opioid use - despite warnings that the drugs are generally not recommended for the management of chronic pain and ongoing concerns of addiction, new research shows.

“This high level of opioid use supports that better pain management treatment options, including nonpharmacological options, are needed for people with MS and pain,” wrote the authors of the study, which was presented at ACTRIMS Forum 2021, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Previous research has shown that more than 50% of people with MS report chronic pain that is serious enough to interfere with daily activities, employment, and quality of life. Many with MS report that pain is one of their worst symptoms, the authors noted.

With surprisingly few studies evaluating opioid use in the MS population, Cinda L. Hugos, PT, associate professor of neurology with the VA Portland Health Care System and the department of neurology, Oregon Health and Science University, Portland, and colleagues investigated the issue in a sample of patients participating in a U.S. multisite MS fatigue management trial conducted between 2013 and 2014.

Of the 281 participants with MS in the study, 58 patients (20.6%) reported using prescription opioids. Among them, most – 44 (76%) – reported regular daily use, 10 (17%) reported using the drugs only as needed, 3 (5%) reported only short-term use, including after recent injury or dental surgery, and 1 provided incomplete information.

Those who reported opioid use had significantly worse fatigue scores on the Modified Fatigue Impact Scale (P = .015) and worse pain scores (P < .0001).

There were no significant differences in terms of age (mean age, 53 years), gender (69% were female), or race (in both groups, about 76% were White). No significant differences were seen in disability or depression scores in the opioid users versus nonusers.

“In this sample of people with multiple sclerosis who self-reported fatigue and volunteered to join an MS fatigue management research study, more than one in five reported using prescription opioids and nearly one in six used opioids daily,” the authors wrote. “Opioid users had more pain and fatigue than nonusers.”

Commenting on the study, Jeffrey Cohen, MD, president of ACTRIMS, said that the findings are consistent with his observations that “in the general population, opioids often are used to treat chronic pain in people with MS.”

But they’re not getting the drugs from his clinic. “We do not prescribe opioids in our clinic, referring such patients to a chronic pain program,” Dr. Cohen said. “However, there clearly is need for better treatment options.”

A previous study on opioid use by people with MS, published in 2015, found even higher rates – 42% reported having ever used opioids, and 38% reported currently using opioids.

Although reports of opioid use by patients with MS have been lacking, more has been published on the emerging use of cannabis-related products. One recent study showed that nearly half of people with MS reported using a cannabis-based therapy for nerve-based pain and sleep disturbances.

Although cannabis is considered safer than opioids, the authors noted that it has its own significant drawback – a “paucity of provider guidance.”

“The range of perceived benefits and potential differential effects of THC and cannabinoid highlight the need for personalized, evidence-based guidelines regarding cannabinoid use,” they wrote.
 

Stretching program for spasticity shows benefits

With spasticity representing a key contributor to MS pain and affecting more than 80% of people with MS, Ms. Hugos and colleagues are developing an alternative to medication – a nonpharmacologic stretching regimen called Spasticity: Take Control” (STC).

Based on evidence-based strategies for the treatment of spasticity in MS, the program involves exercises with daily routines of 15-20 minutes over 6 months.

In a pilot study of 66 patients, also presented at the ACTRIMS meeting, the investigators reported that the program showed significant reductions in pain severity and interference, measured with the Brief Pain Inventory–Short Form, compared with a control consisting of range of motion instruction over 6 months.

The study also offered insights on the specific areas of pain. Among those who reported chronic pain (42% in the STC group and 63.3% in the range-of-motion group), the pain was most frequently reported in the lower back (74.3%), legs (68.6%), or lower back and legs (88.6%).

Ms. Hugos noted that the findings suggest a potentially important nonpharmacologic alternative to spasticity-related pain in MS.

“Stretching is the cornerstone treatment for spasticity from all causes, but there is very little information on stretching exercises in MS or any other conditions,” Ms. Hugos said. “[Our] pilot study is the first and only study using a standardized, daily stretching exercise program to treat MS spasticity,” she said.

“A fully powered study is needed to better understand the impact of different types of exercise on pain severity and interference in multiple sclerosis,” she noted.

Ms. Hugos has received consulting fees from Greenwich Biosciences, Evidera, and Techspert.io. Dr. Cohen has received personal compensation for consulting for Adamas, Atara, Bristol-Myers Squibb, Convelo, MedDay, and Mylan.

A version of this article first appeared on Medscape.com.

With chronic pain common among people with multiple sclerosis (MS), approximately 20% of patients report opioid use - despite warnings that the drugs are generally not recommended for the management of chronic pain and ongoing concerns of addiction, new research shows.

“This high level of opioid use supports that better pain management treatment options, including nonpharmacological options, are needed for people with MS and pain,” wrote the authors of the study, which was presented at ACTRIMS Forum 2021, held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Previous research has shown that more than 50% of people with MS report chronic pain that is serious enough to interfere with daily activities, employment, and quality of life. Many with MS report that pain is one of their worst symptoms, the authors noted.

With surprisingly few studies evaluating opioid use in the MS population, Cinda L. Hugos, PT, associate professor of neurology with the VA Portland Health Care System and the department of neurology, Oregon Health and Science University, Portland, and colleagues investigated the issue in a sample of patients participating in a U.S. multisite MS fatigue management trial conducted between 2013 and 2014.

Of the 281 participants with MS in the study, 58 patients (20.6%) reported using prescription opioids. Among them, most – 44 (76%) – reported regular daily use, 10 (17%) reported using the drugs only as needed, 3 (5%) reported only short-term use, including after recent injury or dental surgery, and 1 provided incomplete information.

Those who reported opioid use had significantly worse fatigue scores on the Modified Fatigue Impact Scale (P = .015) and worse pain scores (P < .0001).

There were no significant differences in terms of age (mean age, 53 years), gender (69% were female), or race (in both groups, about 76% were White). No significant differences were seen in disability or depression scores in the opioid users versus nonusers.

“In this sample of people with multiple sclerosis who self-reported fatigue and volunteered to join an MS fatigue management research study, more than one in five reported using prescription opioids and nearly one in six used opioids daily,” the authors wrote. “Opioid users had more pain and fatigue than nonusers.”

Commenting on the study, Jeffrey Cohen, MD, president of ACTRIMS, said that the findings are consistent with his observations that “in the general population, opioids often are used to treat chronic pain in people with MS.”

But they’re not getting the drugs from his clinic. “We do not prescribe opioids in our clinic, referring such patients to a chronic pain program,” Dr. Cohen said. “However, there clearly is need for better treatment options.”

A previous study on opioid use by people with MS, published in 2015, found even higher rates – 42% reported having ever used opioids, and 38% reported currently using opioids.

Although reports of opioid use by patients with MS have been lacking, more has been published on the emerging use of cannabis-related products. One recent study showed that nearly half of people with MS reported using a cannabis-based therapy for nerve-based pain and sleep disturbances.

Although cannabis is considered safer than opioids, the authors noted that it has its own significant drawback – a “paucity of provider guidance.”

“The range of perceived benefits and potential differential effects of THC and cannabinoid highlight the need for personalized, evidence-based guidelines regarding cannabinoid use,” they wrote.
 

Stretching program for spasticity shows benefits

With spasticity representing a key contributor to MS pain and affecting more than 80% of people with MS, Ms. Hugos and colleagues are developing an alternative to medication – a nonpharmacologic stretching regimen called Spasticity: Take Control” (STC).

Based on evidence-based strategies for the treatment of spasticity in MS, the program involves exercises with daily routines of 15-20 minutes over 6 months.

In a pilot study of 66 patients, also presented at the ACTRIMS meeting, the investigators reported that the program showed significant reductions in pain severity and interference, measured with the Brief Pain Inventory–Short Form, compared with a control consisting of range of motion instruction over 6 months.

The study also offered insights on the specific areas of pain. Among those who reported chronic pain (42% in the STC group and 63.3% in the range-of-motion group), the pain was most frequently reported in the lower back (74.3%), legs (68.6%), or lower back and legs (88.6%).

Ms. Hugos noted that the findings suggest a potentially important nonpharmacologic alternative to spasticity-related pain in MS.

“Stretching is the cornerstone treatment for spasticity from all causes, but there is very little information on stretching exercises in MS or any other conditions,” Ms. Hugos said. “[Our] pilot study is the first and only study using a standardized, daily stretching exercise program to treat MS spasticity,” she said.

“A fully powered study is needed to better understand the impact of different types of exercise on pain severity and interference in multiple sclerosis,” she noted.

Ms. Hugos has received consulting fees from Greenwich Biosciences, Evidera, and Techspert.io. Dr. Cohen has received personal compensation for consulting for Adamas, Atara, Bristol-Myers Squibb, Convelo, MedDay, and Mylan.

A version of this article first appeared on Medscape.com.

Stroke, dementias, and migraine cause the most disability among neurological disorders in the United States, according to new findings derived from the 2017 Global Burden of Disease study. 

The authors of the analysis, led by Valery Feigin, MD, PhD, of New Zealand’s National Institute for Stroke and Applied Neurosciences, and published in the February 2021 issue of JAMA Neurology, looked at prevalence, incidence, mortality, and disability-adjusted life years for 14 neurological disorders across 50 states between 1990 and 2017. The diseases included in the analysis were stroke, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, headaches, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.
 

Tracking the burden of neurologic diseases

Dr. Feigin and colleagues estimated that a full 60% of the U.S. population lives with one or more of these disorders, a figure much greater than previous estimates for neurological disease burden nationwide. Tension-type headache and migraine were the most prevalent in the analysis by Dr. Feigin and colleagues. During the study period, they found, prevalence, incidence, and disability burden of nearly all the included disorders increased, with the exception of brain and spinal cord injuries, meningitis, and encephalitis.

The researchers attributed most of the rise in noncommunicable neurological diseases to population aging. An age-standardized analysis found trends for stroke and Alzheimer’s disease and other dementias to be declining or flat. Age-standardized stroke incidence dropped by 16% from 1990 to 2017, while stroke mortality declined by nearly a third, and stroke disability by a quarter. Age-standardized incidence of Alzheimer’s disease and other dementias dropped by 12%, and their prevalence by 13%, during the study period, though dementia mortality and disability were seen increasing.

The authors surmised that the age-standardized declines in stroke and dementias could reflect that “primary prevention of these disorders are beginning to show an influence.” With dementia, which is linked to cognitive reserve and education, “improving educational levels of cohort reaching the age groups at greatest risk of disease may also be contributing to a modest decline over time,” Dr. Feigin and his colleagues wrote.

Parkinson’s disease and multiple sclerosis, meanwhile, were both seen rising in incidence, prevalence, and disability adjusted life years (DALYs) even with age-standardized figures. The United States saw comparatively more disability in 2017 from dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, and headache disorders, which together comprised 6.7% of DALYs, compared with 4.4% globally; these also accounted for a higher share of mortality in the U.S. than worldwide. The authors attributed at least some of the difference to better case ascertainment in the U.S.
 

Regional variations

The researchers also reported variations in disease burden by state and region. While previous studies have identified a “stroke belt” concentrated in North Carolina, South Carolina, and Georgia, the new findings point to stroke disability highest in Alabama, Arkansas, and Mississippi, and mortality highest in Alabama, Mississippi, and South Carolina. The researchers noted increases in dementia mortality in these states, “likely attributable to the reciprocal association between stroke and dementia.”

Northern states saw higher burdens of multiple sclerosis compared with the rest of the country, while eastern states had higher rates of Parkinson’s disease.

Such regional and state-by state variations, Dr. Feigin and colleagues wrote in their analysis, “may be associated with differences in the case ascertainment, as well as access to health care; racial/ethnic, genetic, and socioeconomic diversity; quality and comprehensiveness of preventive strategies; and risk factor distribution.”

The researchers noted as a limitation of their study that the 14 diseases captured were not an exhaustive list of neurological conditions; chronic lower back pain, a condition included in a previous major study of the burden of neurological disease in the United States, was omitted, as were restless legs syndrome and peripheral neuropathy. The researchers cited changes to coding practice in the U.S. and accuracy of medical claims data as potential limitations of their analysis. The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation, and several of Dr. Feigin’s coauthors reported financial relationships with industry.
 

Time to adjust the stroke belt?

Amelia Boehme, PhD, a stroke epidemiologist at Columbia University Mailman School of Public Health in New York, said in an interview that the current study added to recent findings showing surprising local variability in stroke prevalence, incidence, and mortality. “What we had always conceptually thought of as the ‘stroke belt’ isn’t necessarily the case,” Dr. Boehme said, but is rather subject to local, county-by-county variations. “Looking at the data here in conjunction with what previous authors have found, it raises some questions as to whether or not state-level data is giving a completely accurate picture, and whether we need to start looking at the county level and adjust for populations and age.” Importantly, Dr. Boehme said, data collected in the Global Burden of Disease study tends to be exceptionally rigorous and systematic, adding weight to Dr. Feigin and colleagues’ suggestions that prevention efforts may be making a dent in stroke and dementia. 

“More data is always needed before we start to say we’re seeing things change,” Dr. Boehme noted. “But any glimmer of optimism is welcome, especially with regard to interventions that have been put in place, to allow us to build on those interventions.”

Dr. Boehme disclosed no financial conflicts of interest.

Stroke, dementias, and migraine cause the most disability among neurological disorders in the United States, according to new findings derived from the 2017 Global Burden of Disease study. 

The authors of the analysis, led by Valery Feigin, MD, PhD, of New Zealand’s National Institute for Stroke and Applied Neurosciences, and published in the February 2021 issue of JAMA Neurology, looked at prevalence, incidence, mortality, and disability-adjusted life years for 14 neurological disorders across 50 states between 1990 and 2017. The diseases included in the analysis were stroke, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, headaches, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.
 

Tracking the burden of neurologic diseases

Dr. Feigin and colleagues estimated that a full 60% of the U.S. population lives with one or more of these disorders, a figure much greater than previous estimates for neurological disease burden nationwide. Tension-type headache and migraine were the most prevalent in the analysis by Dr. Feigin and colleagues. During the study period, they found, prevalence, incidence, and disability burden of nearly all the included disorders increased, with the exception of brain and spinal cord injuries, meningitis, and encephalitis.

The researchers attributed most of the rise in noncommunicable neurological diseases to population aging. An age-standardized analysis found trends for stroke and Alzheimer’s disease and other dementias to be declining or flat. Age-standardized stroke incidence dropped by 16% from 1990 to 2017, while stroke mortality declined by nearly a third, and stroke disability by a quarter. Age-standardized incidence of Alzheimer’s disease and other dementias dropped by 12%, and their prevalence by 13%, during the study period, though dementia mortality and disability were seen increasing.

The authors surmised that the age-standardized declines in stroke and dementias could reflect that “primary prevention of these disorders are beginning to show an influence.” With dementia, which is linked to cognitive reserve and education, “improving educational levels of cohort reaching the age groups at greatest risk of disease may also be contributing to a modest decline over time,” Dr. Feigin and his colleagues wrote.

Parkinson’s disease and multiple sclerosis, meanwhile, were both seen rising in incidence, prevalence, and disability adjusted life years (DALYs) even with age-standardized figures. The United States saw comparatively more disability in 2017 from dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, and headache disorders, which together comprised 6.7% of DALYs, compared with 4.4% globally; these also accounted for a higher share of mortality in the U.S. than worldwide. The authors attributed at least some of the difference to better case ascertainment in the U.S.
 

Regional variations

The researchers also reported variations in disease burden by state and region. While previous studies have identified a “stroke belt” concentrated in North Carolina, South Carolina, and Georgia, the new findings point to stroke disability highest in Alabama, Arkansas, and Mississippi, and mortality highest in Alabama, Mississippi, and South Carolina. The researchers noted increases in dementia mortality in these states, “likely attributable to the reciprocal association between stroke and dementia.”

Northern states saw higher burdens of multiple sclerosis compared with the rest of the country, while eastern states had higher rates of Parkinson’s disease.

Such regional and state-by state variations, Dr. Feigin and colleagues wrote in their analysis, “may be associated with differences in the case ascertainment, as well as access to health care; racial/ethnic, genetic, and socioeconomic diversity; quality and comprehensiveness of preventive strategies; and risk factor distribution.”

The researchers noted as a limitation of their study that the 14 diseases captured were not an exhaustive list of neurological conditions; chronic lower back pain, a condition included in a previous major study of the burden of neurological disease in the United States, was omitted, as were restless legs syndrome and peripheral neuropathy. The researchers cited changes to coding practice in the U.S. and accuracy of medical claims data as potential limitations of their analysis. The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation, and several of Dr. Feigin’s coauthors reported financial relationships with industry.
 

Time to adjust the stroke belt?

Amelia Boehme, PhD, a stroke epidemiologist at Columbia University Mailman School of Public Health in New York, said in an interview that the current study added to recent findings showing surprising local variability in stroke prevalence, incidence, and mortality. “What we had always conceptually thought of as the ‘stroke belt’ isn’t necessarily the case,” Dr. Boehme said, but is rather subject to local, county-by-county variations. “Looking at the data here in conjunction with what previous authors have found, it raises some questions as to whether or not state-level data is giving a completely accurate picture, and whether we need to start looking at the county level and adjust for populations and age.” Importantly, Dr. Boehme said, data collected in the Global Burden of Disease study tends to be exceptionally rigorous and systematic, adding weight to Dr. Feigin and colleagues’ suggestions that prevention efforts may be making a dent in stroke and dementia. 

“More data is always needed before we start to say we’re seeing things change,” Dr. Boehme noted. “But any glimmer of optimism is welcome, especially with regard to interventions that have been put in place, to allow us to build on those interventions.”

Dr. Boehme disclosed no financial conflicts of interest.

Stroke, dementias, and migraine cause the most disability among neurological disorders in the United States, according to new findings derived from the 2017 Global Burden of Disease study. 

The authors of the analysis, led by Valery Feigin, MD, PhD, of New Zealand’s National Institute for Stroke and Applied Neurosciences, and published in the February 2021 issue of JAMA Neurology, looked at prevalence, incidence, mortality, and disability-adjusted life years for 14 neurological disorders across 50 states between 1990 and 2017. The diseases included in the analysis were stroke, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, headaches, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.
 

Tracking the burden of neurologic diseases

Dr. Feigin and colleagues estimated that a full 60% of the U.S. population lives with one or more of these disorders, a figure much greater than previous estimates for neurological disease burden nationwide. Tension-type headache and migraine were the most prevalent in the analysis by Dr. Feigin and colleagues. During the study period, they found, prevalence, incidence, and disability burden of nearly all the included disorders increased, with the exception of brain and spinal cord injuries, meningitis, and encephalitis.

The researchers attributed most of the rise in noncommunicable neurological diseases to population aging. An age-standardized analysis found trends for stroke and Alzheimer’s disease and other dementias to be declining or flat. Age-standardized stroke incidence dropped by 16% from 1990 to 2017, while stroke mortality declined by nearly a third, and stroke disability by a quarter. Age-standardized incidence of Alzheimer’s disease and other dementias dropped by 12%, and their prevalence by 13%, during the study period, though dementia mortality and disability were seen increasing.

The authors surmised that the age-standardized declines in stroke and dementias could reflect that “primary prevention of these disorders are beginning to show an influence.” With dementia, which is linked to cognitive reserve and education, “improving educational levels of cohort reaching the age groups at greatest risk of disease may also be contributing to a modest decline over time,” Dr. Feigin and his colleagues wrote.

Parkinson’s disease and multiple sclerosis, meanwhile, were both seen rising in incidence, prevalence, and disability adjusted life years (DALYs) even with age-standardized figures. The United States saw comparatively more disability in 2017 from dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, and headache disorders, which together comprised 6.7% of DALYs, compared with 4.4% globally; these also accounted for a higher share of mortality in the U.S. than worldwide. The authors attributed at least some of the difference to better case ascertainment in the U.S.
 

Regional variations

The researchers also reported variations in disease burden by state and region. While previous studies have identified a “stroke belt” concentrated in North Carolina, South Carolina, and Georgia, the new findings point to stroke disability highest in Alabama, Arkansas, and Mississippi, and mortality highest in Alabama, Mississippi, and South Carolina. The researchers noted increases in dementia mortality in these states, “likely attributable to the reciprocal association between stroke and dementia.”

Northern states saw higher burdens of multiple sclerosis compared with the rest of the country, while eastern states had higher rates of Parkinson’s disease.

Such regional and state-by state variations, Dr. Feigin and colleagues wrote in their analysis, “may be associated with differences in the case ascertainment, as well as access to health care; racial/ethnic, genetic, and socioeconomic diversity; quality and comprehensiveness of preventive strategies; and risk factor distribution.”

The researchers noted as a limitation of their study that the 14 diseases captured were not an exhaustive list of neurological conditions; chronic lower back pain, a condition included in a previous major study of the burden of neurological disease in the United States, was omitted, as were restless legs syndrome and peripheral neuropathy. The researchers cited changes to coding practice in the U.S. and accuracy of medical claims data as potential limitations of their analysis. The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation, and several of Dr. Feigin’s coauthors reported financial relationships with industry.
 

Time to adjust the stroke belt?

Amelia Boehme, PhD, a stroke epidemiologist at Columbia University Mailman School of Public Health in New York, said in an interview that the current study added to recent findings showing surprising local variability in stroke prevalence, incidence, and mortality. “What we had always conceptually thought of as the ‘stroke belt’ isn’t necessarily the case,” Dr. Boehme said, but is rather subject to local, county-by-county variations. “Looking at the data here in conjunction with what previous authors have found, it raises some questions as to whether or not state-level data is giving a completely accurate picture, and whether we need to start looking at the county level and adjust for populations and age.” Importantly, Dr. Boehme said, data collected in the Global Burden of Disease study tends to be exceptionally rigorous and systematic, adding weight to Dr. Feigin and colleagues’ suggestions that prevention efforts may be making a dent in stroke and dementia. 

“More data is always needed before we start to say we’re seeing things change,” Dr. Boehme noted. “But any glimmer of optimism is welcome, especially with regard to interventions that have been put in place, to allow us to build on those interventions.”

Dr. Boehme disclosed no financial conflicts of interest.

Multiple sclerosis (MS) may not pose a higher risk for complications in pregnant women, according to a new study published online Feb. 3 in Neurology Clinical Practice. While pregnancy and childbirth are not regarded as conditions that engender high-risk pregnancy in the MS population, previous studies evaluating the effects of MS on pregnancy and parturition have yet to fully elucidate some outcomes for pregnant women and their babies in multiple sclerosis.

“Women with multiple sclerosis may be understandably concerned about the risk of pregnancy,” said Melinda Magyari, MD, PhD, a consultant at the University of Copenhagen. “While previous research has shown there is no higher risk of birth defect for babies born to women with MS, we wanted to find out if women with MS are at risk for a variety of pregnancy complications.”

MS is regarded as a progressive, neurological disease mediated by the immune system that demands careful consideration of numerous situations and life changes including family planning. The MS population is overwhelmingly female, as women account for three out of every four cases of MS. The majority of these women range from 20 to 40 years of age at the time of being diagnosed with MS. Despite the unknown risks of pregnancy-related complications and various perinatal complications in this patient population, women who have MS are not discouraged from conceiving.
 

Assessing pregnancy outcomes

This nationwide, population-based, cross-sectional study evaluated the pregnancies of 2,930 women with MS between Jan. 1, 1997, and Dec. 31, 2016, registered in the Danish Multiple Sclerosis Registry. The researchers compared pregnancy-related and prenatal outcomes to a 5% random sample of 56,958 randomly-selected pregnant women from Denmark’s general population who did not have MS. They found no differences in the risks associated with several pregnancy-related complications (e.g., preeclampsia, gestational diabetes, or placental complications), emergency Cesarean section (C-section), instrumental delivery, stillbirth, preterm birth, or congenital malformation. Apgar scores were low in both groups. A composite of various biometrics in newborns such as reflexes, muscle tone, and heart rate immediately following birth, the Apgar score is used to help assess the neonatal health, with a value of less than 7 considered low. Here, preterm birth is defined as delivery occurring before 37 weeks of gestation, and stillbirth describes a fetus born dead after 22 weeks of gestation.

Women in the MS cohort were more likely to have elective C-sections (odds ratio, 2.89 [95% confidence interval, 1.65-2.16]), induced labor (OR, 1.15 [95%CI, 1.01-1.31]) and have babies with low birth weight based on their gestational age (OR, 1.29 [95% CI, 1.04-1.60]). Nearly 30% of babies born in the cohort (n = 851) were born to mothers who had received disease-modifying therapy (DMT). Neonates exposed to DMT weighed an average of 116 g less than babies born to mothers who had not received DMT (3,378 g vs. 3,494 g) with a slightly lower gestational age (39 weeks as opposed to 40 weeks). However, babies born to mothers with MS were less likely to show signs of asphyxia (OR, 0.87 [95% CI, 0.78-0.97]) than the comparison cohort.

“We found overall, their pregnancies were just as healthy as those of the moms without MS,” Dr. Magyari said.
 

Comprehensive data

Denmark’s health care system has two key features that make it an attractive setting in which to conduct such a study – the first being its universal health care. The second advantage is that the country enacted several health registries in the 1970s and 1980s that enable the collection of more comprehensive data. For example, the Danish National Patient Register is a population-based registry that spans the entire nation, facilitating epidemiological research with what the study’s authors describe as “high generalizability.” Providing additional insights regarding the patient story helps add context to pregnancy and outcomes. Among the data collected on the women studied were demographics, contact information, and abortions, both spontaneous and medically induced. The country uses other databases and registries to capture additional data. For example, the Register of Legally Induced Abortions provides data regarding the context of medically induced abortions. In contrast, the Danish Medical Birth Registry provides context regarding specified variables regarding women’s pregnancies, delivery, and perinatal outcomes. Finally, the population’s education register offers information regarding patients’ educational history.

A key strength of this study is that the long duration of follow-up data from the Danish Medical Birth Registry, along with its comprehensive data collection, eliminates recall bias. Universal access to health care also improves the generalizability of data. A limitation of the study is its lack of data on maternal smoking and its effects on low gestational weights. The study also has some data gaps, including body mass index information missing from a large portion of the cohort. Finally, the sample size of newborns born to mothers who had received DMT therapy within the last 6 months of gestation was too underpowered to stratify based on first on first-line or second-line treatment.

Dr. Magyari served on scientific advisory boards for Biogen, Sanofi, Teva, Roche, Novartis, and Merck. She has also received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, and has received research support and support for congress participation from Biogen, Genzyme, Teva, Roche, Merck, and Novartis. Coauthors disclosed various fees received from Merck, Novartis, Biogen, Roche, Sanofi Genzyme, and Teva.

Multiple sclerosis (MS) may not pose a higher risk for complications in pregnant women, according to a new study published online Feb. 3 in Neurology Clinical Practice. While pregnancy and childbirth are not regarded as conditions that engender high-risk pregnancy in the MS population, previous studies evaluating the effects of MS on pregnancy and parturition have yet to fully elucidate some outcomes for pregnant women and their babies in multiple sclerosis.

“Women with multiple sclerosis may be understandably concerned about the risk of pregnancy,” said Melinda Magyari, MD, PhD, a consultant at the University of Copenhagen. “While previous research has shown there is no higher risk of birth defect for babies born to women with MS, we wanted to find out if women with MS are at risk for a variety of pregnancy complications.”

MS is regarded as a progressive, neurological disease mediated by the immune system that demands careful consideration of numerous situations and life changes including family planning. The MS population is overwhelmingly female, as women account for three out of every four cases of MS. The majority of these women range from 20 to 40 years of age at the time of being diagnosed with MS. Despite the unknown risks of pregnancy-related complications and various perinatal complications in this patient population, women who have MS are not discouraged from conceiving.
 

Assessing pregnancy outcomes

This nationwide, population-based, cross-sectional study evaluated the pregnancies of 2,930 women with MS between Jan. 1, 1997, and Dec. 31, 2016, registered in the Danish Multiple Sclerosis Registry. The researchers compared pregnancy-related and prenatal outcomes to a 5% random sample of 56,958 randomly-selected pregnant women from Denmark’s general population who did not have MS. They found no differences in the risks associated with several pregnancy-related complications (e.g., preeclampsia, gestational diabetes, or placental complications), emergency Cesarean section (C-section), instrumental delivery, stillbirth, preterm birth, or congenital malformation. Apgar scores were low in both groups. A composite of various biometrics in newborns such as reflexes, muscle tone, and heart rate immediately following birth, the Apgar score is used to help assess the neonatal health, with a value of less than 7 considered low. Here, preterm birth is defined as delivery occurring before 37 weeks of gestation, and stillbirth describes a fetus born dead after 22 weeks of gestation.

Women in the MS cohort were more likely to have elective C-sections (odds ratio, 2.89 [95% confidence interval, 1.65-2.16]), induced labor (OR, 1.15 [95%CI, 1.01-1.31]) and have babies with low birth weight based on their gestational age (OR, 1.29 [95% CI, 1.04-1.60]). Nearly 30% of babies born in the cohort (n = 851) were born to mothers who had received disease-modifying therapy (DMT). Neonates exposed to DMT weighed an average of 116 g less than babies born to mothers who had not received DMT (3,378 g vs. 3,494 g) with a slightly lower gestational age (39 weeks as opposed to 40 weeks). However, babies born to mothers with MS were less likely to show signs of asphyxia (OR, 0.87 [95% CI, 0.78-0.97]) than the comparison cohort.

“We found overall, their pregnancies were just as healthy as those of the moms without MS,” Dr. Magyari said.
 

Comprehensive data

Denmark’s health care system has two key features that make it an attractive setting in which to conduct such a study – the first being its universal health care. The second advantage is that the country enacted several health registries in the 1970s and 1980s that enable the collection of more comprehensive data. For example, the Danish National Patient Register is a population-based registry that spans the entire nation, facilitating epidemiological research with what the study’s authors describe as “high generalizability.” Providing additional insights regarding the patient story helps add context to pregnancy and outcomes. Among the data collected on the women studied were demographics, contact information, and abortions, both spontaneous and medically induced. The country uses other databases and registries to capture additional data. For example, the Register of Legally Induced Abortions provides data regarding the context of medically induced abortions. In contrast, the Danish Medical Birth Registry provides context regarding specified variables regarding women’s pregnancies, delivery, and perinatal outcomes. Finally, the population’s education register offers information regarding patients’ educational history.

A key strength of this study is that the long duration of follow-up data from the Danish Medical Birth Registry, along with its comprehensive data collection, eliminates recall bias. Universal access to health care also improves the generalizability of data. A limitation of the study is its lack of data on maternal smoking and its effects on low gestational weights. The study also has some data gaps, including body mass index information missing from a large portion of the cohort. Finally, the sample size of newborns born to mothers who had received DMT therapy within the last 6 months of gestation was too underpowered to stratify based on first on first-line or second-line treatment.

Dr. Magyari served on scientific advisory boards for Biogen, Sanofi, Teva, Roche, Novartis, and Merck. She has also received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, and has received research support and support for congress participation from Biogen, Genzyme, Teva, Roche, Merck, and Novartis. Coauthors disclosed various fees received from Merck, Novartis, Biogen, Roche, Sanofi Genzyme, and Teva.

Multiple sclerosis (MS) may not pose a higher risk for complications in pregnant women, according to a new study published online Feb. 3 in Neurology Clinical Practice. While pregnancy and childbirth are not regarded as conditions that engender high-risk pregnancy in the MS population, previous studies evaluating the effects of MS on pregnancy and parturition have yet to fully elucidate some outcomes for pregnant women and their babies in multiple sclerosis.

“Women with multiple sclerosis may be understandably concerned about the risk of pregnancy,” said Melinda Magyari, MD, PhD, a consultant at the University of Copenhagen. “While previous research has shown there is no higher risk of birth defect for babies born to women with MS, we wanted to find out if women with MS are at risk for a variety of pregnancy complications.”

MS is regarded as a progressive, neurological disease mediated by the immune system that demands careful consideration of numerous situations and life changes including family planning. The MS population is overwhelmingly female, as women account for three out of every four cases of MS. The majority of these women range from 20 to 40 years of age at the time of being diagnosed with MS. Despite the unknown risks of pregnancy-related complications and various perinatal complications in this patient population, women who have MS are not discouraged from conceiving.
 

Assessing pregnancy outcomes

This nationwide, population-based, cross-sectional study evaluated the pregnancies of 2,930 women with MS between Jan. 1, 1997, and Dec. 31, 2016, registered in the Danish Multiple Sclerosis Registry. The researchers compared pregnancy-related and prenatal outcomes to a 5% random sample of 56,958 randomly-selected pregnant women from Denmark’s general population who did not have MS. They found no differences in the risks associated with several pregnancy-related complications (e.g., preeclampsia, gestational diabetes, or placental complications), emergency Cesarean section (C-section), instrumental delivery, stillbirth, preterm birth, or congenital malformation. Apgar scores were low in both groups. A composite of various biometrics in newborns such as reflexes, muscle tone, and heart rate immediately following birth, the Apgar score is used to help assess the neonatal health, with a value of less than 7 considered low. Here, preterm birth is defined as delivery occurring before 37 weeks of gestation, and stillbirth describes a fetus born dead after 22 weeks of gestation.

Women in the MS cohort were more likely to have elective C-sections (odds ratio, 2.89 [95% confidence interval, 1.65-2.16]), induced labor (OR, 1.15 [95%CI, 1.01-1.31]) and have babies with low birth weight based on their gestational age (OR, 1.29 [95% CI, 1.04-1.60]). Nearly 30% of babies born in the cohort (n = 851) were born to mothers who had received disease-modifying therapy (DMT). Neonates exposed to DMT weighed an average of 116 g less than babies born to mothers who had not received DMT (3,378 g vs. 3,494 g) with a slightly lower gestational age (39 weeks as opposed to 40 weeks). However, babies born to mothers with MS were less likely to show signs of asphyxia (OR, 0.87 [95% CI, 0.78-0.97]) than the comparison cohort.

“We found overall, their pregnancies were just as healthy as those of the moms without MS,” Dr. Magyari said.
 

Comprehensive data

Denmark’s health care system has two key features that make it an attractive setting in which to conduct such a study – the first being its universal health care. The second advantage is that the country enacted several health registries in the 1970s and 1980s that enable the collection of more comprehensive data. For example, the Danish National Patient Register is a population-based registry that spans the entire nation, facilitating epidemiological research with what the study’s authors describe as “high generalizability.” Providing additional insights regarding the patient story helps add context to pregnancy and outcomes. Among the data collected on the women studied were demographics, contact information, and abortions, both spontaneous and medically induced. The country uses other databases and registries to capture additional data. For example, the Register of Legally Induced Abortions provides data regarding the context of medically induced abortions. In contrast, the Danish Medical Birth Registry provides context regarding specified variables regarding women’s pregnancies, delivery, and perinatal outcomes. Finally, the population’s education register offers information regarding patients’ educational history.

A key strength of this study is that the long duration of follow-up data from the Danish Medical Birth Registry, along with its comprehensive data collection, eliminates recall bias. Universal access to health care also improves the generalizability of data. A limitation of the study is its lack of data on maternal smoking and its effects on low gestational weights. The study also has some data gaps, including body mass index information missing from a large portion of the cohort. Finally, the sample size of newborns born to mothers who had received DMT therapy within the last 6 months of gestation was too underpowered to stratify based on first on first-line or second-line treatment.

Dr. Magyari served on scientific advisory boards for Biogen, Sanofi, Teva, Roche, Novartis, and Merck. She has also received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, and has received research support and support for congress participation from Biogen, Genzyme, Teva, Roche, Merck, and Novartis. Coauthors disclosed various fees received from Merck, Novartis, Biogen, Roche, Sanofi Genzyme, and Teva.

The Food and Drug Administration has approved intramuscular (IM) administration of peginterferon beta-1a (Plegridy, Biogen) for patients with relapsing forms of multiple sclerosis (MS).

“The new IM administration offers people living with relapsing MS the well-characterized efficacy and safety of Plegridy with the potential for significantly reduced injection site reactions,” Biogen said in a news release announcing the FDA action.

Plegridy is a pegylated version of interferon beta-1a, which prolongs the circulation time of the molecule in the body by increasing its size. The process extends the drug’s half-life, allowing for a less-frequent dosing schedule.

Peginterferon beta-1a administered subcutaneously was first approved by the FDA in 2014 based on data showing it significantly reduces MS relapses, disability progression, and brain lesions.

The FDA approved IM administration for peginterferon beta-1a based on data evaluating bioequivalence and adverse reactions associated with IM administration compared with subcutaneous (SC) administration in healthy volunteers.

Bioequivalence of the IM and SC dosing regimens was confirmed and volunteers receiving the drug through IM administration experienced fewer injection site reactions relative to those receiving SC administration (14.4% vs. 32.1%), the company said.

The overall safety profiles of IM and SC administration were generally similar, with no new safety signals.

The European Commission allowed marketing authorization for IM administration of peginterferon beta-1a in December 2020.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved intramuscular (IM) administration of peginterferon beta-1a (Plegridy, Biogen) for patients with relapsing forms of multiple sclerosis (MS).

“The new IM administration offers people living with relapsing MS the well-characterized efficacy and safety of Plegridy with the potential for significantly reduced injection site reactions,” Biogen said in a news release announcing the FDA action.

Plegridy is a pegylated version of interferon beta-1a, which prolongs the circulation time of the molecule in the body by increasing its size. The process extends the drug’s half-life, allowing for a less-frequent dosing schedule.

Peginterferon beta-1a administered subcutaneously was first approved by the FDA in 2014 based on data showing it significantly reduces MS relapses, disability progression, and brain lesions.

The FDA approved IM administration for peginterferon beta-1a based on data evaluating bioequivalence and adverse reactions associated with IM administration compared with subcutaneous (SC) administration in healthy volunteers.

Bioequivalence of the IM and SC dosing regimens was confirmed and volunteers receiving the drug through IM administration experienced fewer injection site reactions relative to those receiving SC administration (14.4% vs. 32.1%), the company said.

The overall safety profiles of IM and SC administration were generally similar, with no new safety signals.

The European Commission allowed marketing authorization for IM administration of peginterferon beta-1a in December 2020.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved intramuscular (IM) administration of peginterferon beta-1a (Plegridy, Biogen) for patients with relapsing forms of multiple sclerosis (MS).

“The new IM administration offers people living with relapsing MS the well-characterized efficacy and safety of Plegridy with the potential for significantly reduced injection site reactions,” Biogen said in a news release announcing the FDA action.

Plegridy is a pegylated version of interferon beta-1a, which prolongs the circulation time of the molecule in the body by increasing its size. The process extends the drug’s half-life, allowing for a less-frequent dosing schedule.

Peginterferon beta-1a administered subcutaneously was first approved by the FDA in 2014 based on data showing it significantly reduces MS relapses, disability progression, and brain lesions.

The FDA approved IM administration for peginterferon beta-1a based on data evaluating bioequivalence and adverse reactions associated with IM administration compared with subcutaneous (SC) administration in healthy volunteers.

Bioequivalence of the IM and SC dosing regimens was confirmed and volunteers receiving the drug through IM administration experienced fewer injection site reactions relative to those receiving SC administration (14.4% vs. 32.1%), the company said.

The overall safety profiles of IM and SC administration were generally similar, with no new safety signals.

The European Commission allowed marketing authorization for IM administration of peginterferon beta-1a in December 2020.

A version of this article first appeared on Medscape.com.

Clinical trials enrolling patients with progressive multiple sclerosis (MS) commonly use the Expanded Disability Status Scale (EDSS), an instrument that looks at impairment across several different functional domains, as a primary outcome measure. But results from a new analysis of trial data suggest that the EDSS, in use since 1983, may be a noisier or more variation-prone measure of MS disease progression than two other widely used measures: the timed 25-foot walk and the 9-hole peg test.

For their research, published in the Jan. 5 issue of Neurology, Marcus W. Koch, MD, PhD, of the department of neurosciences at Hotchkiss Brain Institute at the University of Calgary (Alta.) and colleagues looked at data from the placebo arms of two randomized trials that collectively enrolled nearly 700 patients with secondary progressive MS (SPMS). The trials were similar in terms of baseline patient characteristics and level of disability.
 

Comparing three outcome measures

The investigators compared disability progression and improvement across each of the three instruments and their combinations. Because improvement is understood to occur only rarely in untreated secondary progressive MS, most improvement picked up in the placebo arm of a trial is assumed to be noise from random variation or measurement error.

Dr. Koch and colleagues found that the EDSS showed higher rates of improvement than the other tests. The EDSS also showed the smallest differences between progression and improvement among the three instruments, with improvement rate over time increasing in parallel with disability progression rates. With the other two tests, improvement rates remained low – at 10% or less – while disability was seen steadily increasing over time.

The results, the investigators wrote in their analysis, suggest that the timed 25-foot walk and 9-hole peg test are the more reliable outcome measures. The reason “may simply lie in the fact that both the timed 25-foot walk and 9-hole peg test are objective and quantitative interval-scaled measures while the EDSS is a graded categorical measure.” As primary outcome measures in clinical trials, “the lower noise of the timed 25-foot walk and 9-hole peg test may make them preferable over the EDSS,” Dr. Koch and colleagues concluded. The investigators noted that a 2019 analysis of different MS disability scales across more than 13,000 patients in 14 trials did not find such stark differences – but that the patients in the pooled trials had less disability at baseline (median EDSS score of 2.5, compared with 6.0 for the two trials in Dr. Koch and colleagues’ study). This suggests, the investigators wrote, “that the timed 25-foot walk and 9-hole peg test may be more useful outcomes in patients with a progressive disease course and with greater baseline disability.”
 

‘Considerable implications’ for the design of future clinical trials

In an accompanying editorial, Tomas Kalincik, MD, PhD, of the University of Melbourne, along with colleagues in Italy and Britain, praised Dr. Koch and colleagues’ study as having “considerable implications for the design of future clinical trials because detecting a treatment effect on an outcome that is subject to large measurement error is difficult.” Most trials in progressive MS use change in EDSS score as their primary or key secondary outcomes. “However, as the authors elegantly show, other, more reliable clinical outcomes are needed. As we are revisiting our biological hypotheses for treatment of progressive MS, perhaps the time has come that we should also revisit the instruments that we use to examine their efficacy.”

The editorialists allowed for the possibility that something besides noise or measurement error could be responsible for the disparities seen across the instruments. “An alternative interpretation of the presented results could be that recovery of neurologic function is more common in SPMS than what we had previously thought and that EDSS is more sensitive to its detection than the other two measures,” they wrote.

Dr. Koch and colleagues’ study received no outside funding. Dr. Koch disclosed consulting fees and other financial support from several drug manufacturers, and three coauthors also disclosed financial relationships with pharmaceutical companies. All three editorial writers disclosed similar relationships.

Clinical trials enrolling patients with progressive multiple sclerosis (MS) commonly use the Expanded Disability Status Scale (EDSS), an instrument that looks at impairment across several different functional domains, as a primary outcome measure. But results from a new analysis of trial data suggest that the EDSS, in use since 1983, may be a noisier or more variation-prone measure of MS disease progression than two other widely used measures: the timed 25-foot walk and the 9-hole peg test.

For their research, published in the Jan. 5 issue of Neurology, Marcus W. Koch, MD, PhD, of the department of neurosciences at Hotchkiss Brain Institute at the University of Calgary (Alta.) and colleagues looked at data from the placebo arms of two randomized trials that collectively enrolled nearly 700 patients with secondary progressive MS (SPMS). The trials were similar in terms of baseline patient characteristics and level of disability.
 

Comparing three outcome measures

The investigators compared disability progression and improvement across each of the three instruments and their combinations. Because improvement is understood to occur only rarely in untreated secondary progressive MS, most improvement picked up in the placebo arm of a trial is assumed to be noise from random variation or measurement error.

Dr. Koch and colleagues found that the EDSS showed higher rates of improvement than the other tests. The EDSS also showed the smallest differences between progression and improvement among the three instruments, with improvement rate over time increasing in parallel with disability progression rates. With the other two tests, improvement rates remained low – at 10% or less – while disability was seen steadily increasing over time.

The results, the investigators wrote in their analysis, suggest that the timed 25-foot walk and 9-hole peg test are the more reliable outcome measures. The reason “may simply lie in the fact that both the timed 25-foot walk and 9-hole peg test are objective and quantitative interval-scaled measures while the EDSS is a graded categorical measure.” As primary outcome measures in clinical trials, “the lower noise of the timed 25-foot walk and 9-hole peg test may make them preferable over the EDSS,” Dr. Koch and colleagues concluded. The investigators noted that a 2019 analysis of different MS disability scales across more than 13,000 patients in 14 trials did not find such stark differences – but that the patients in the pooled trials had less disability at baseline (median EDSS score of 2.5, compared with 6.0 for the two trials in Dr. Koch and colleagues’ study). This suggests, the investigators wrote, “that the timed 25-foot walk and 9-hole peg test may be more useful outcomes in patients with a progressive disease course and with greater baseline disability.”
 

‘Considerable implications’ for the design of future clinical trials

In an accompanying editorial, Tomas Kalincik, MD, PhD, of the University of Melbourne, along with colleagues in Italy and Britain, praised Dr. Koch and colleagues’ study as having “considerable implications for the design of future clinical trials because detecting a treatment effect on an outcome that is subject to large measurement error is difficult.” Most trials in progressive MS use change in EDSS score as their primary or key secondary outcomes. “However, as the authors elegantly show, other, more reliable clinical outcomes are needed. As we are revisiting our biological hypotheses for treatment of progressive MS, perhaps the time has come that we should also revisit the instruments that we use to examine their efficacy.”

The editorialists allowed for the possibility that something besides noise or measurement error could be responsible for the disparities seen across the instruments. “An alternative interpretation of the presented results could be that recovery of neurologic function is more common in SPMS than what we had previously thought and that EDSS is more sensitive to its detection than the other two measures,” they wrote.

Dr. Koch and colleagues’ study received no outside funding. Dr. Koch disclosed consulting fees and other financial support from several drug manufacturers, and three coauthors also disclosed financial relationships with pharmaceutical companies. All three editorial writers disclosed similar relationships.

Clinical trials enrolling patients with progressive multiple sclerosis (MS) commonly use the Expanded Disability Status Scale (EDSS), an instrument that looks at impairment across several different functional domains, as a primary outcome measure. But results from a new analysis of trial data suggest that the EDSS, in use since 1983, may be a noisier or more variation-prone measure of MS disease progression than two other widely used measures: the timed 25-foot walk and the 9-hole peg test.

For their research, published in the Jan. 5 issue of Neurology, Marcus W. Koch, MD, PhD, of the department of neurosciences at Hotchkiss Brain Institute at the University of Calgary (Alta.) and colleagues looked at data from the placebo arms of two randomized trials that collectively enrolled nearly 700 patients with secondary progressive MS (SPMS). The trials were similar in terms of baseline patient characteristics and level of disability.
 

Comparing three outcome measures

The investigators compared disability progression and improvement across each of the three instruments and their combinations. Because improvement is understood to occur only rarely in untreated secondary progressive MS, most improvement picked up in the placebo arm of a trial is assumed to be noise from random variation or measurement error.

Dr. Koch and colleagues found that the EDSS showed higher rates of improvement than the other tests. The EDSS also showed the smallest differences between progression and improvement among the three instruments, with improvement rate over time increasing in parallel with disability progression rates. With the other two tests, improvement rates remained low – at 10% or less – while disability was seen steadily increasing over time.

The results, the investigators wrote in their analysis, suggest that the timed 25-foot walk and 9-hole peg test are the more reliable outcome measures. The reason “may simply lie in the fact that both the timed 25-foot walk and 9-hole peg test are objective and quantitative interval-scaled measures while the EDSS is a graded categorical measure.” As primary outcome measures in clinical trials, “the lower noise of the timed 25-foot walk and 9-hole peg test may make them preferable over the EDSS,” Dr. Koch and colleagues concluded. The investigators noted that a 2019 analysis of different MS disability scales across more than 13,000 patients in 14 trials did not find such stark differences – but that the patients in the pooled trials had less disability at baseline (median EDSS score of 2.5, compared with 6.0 for the two trials in Dr. Koch and colleagues’ study). This suggests, the investigators wrote, “that the timed 25-foot walk and 9-hole peg test may be more useful outcomes in patients with a progressive disease course and with greater baseline disability.”
 

‘Considerable implications’ for the design of future clinical trials

In an accompanying editorial, Tomas Kalincik, MD, PhD, of the University of Melbourne, along with colleagues in Italy and Britain, praised Dr. Koch and colleagues’ study as having “considerable implications for the design of future clinical trials because detecting a treatment effect on an outcome that is subject to large measurement error is difficult.” Most trials in progressive MS use change in EDSS score as their primary or key secondary outcomes. “However, as the authors elegantly show, other, more reliable clinical outcomes are needed. As we are revisiting our biological hypotheses for treatment of progressive MS, perhaps the time has come that we should also revisit the instruments that we use to examine their efficacy.”

The editorialists allowed for the possibility that something besides noise or measurement error could be responsible for the disparities seen across the instruments. “An alternative interpretation of the presented results could be that recovery of neurologic function is more common in SPMS than what we had previously thought and that EDSS is more sensitive to its detection than the other two measures,” they wrote.

Dr. Koch and colleagues’ study received no outside funding. Dr. Koch disclosed consulting fees and other financial support from several drug manufacturers, and three coauthors also disclosed financial relationships with pharmaceutical companies. All three editorial writers disclosed similar relationships.

The benefits of autologous hematopoietic stem cell transplant (AHSCT) for patients with multiple sclerosis (MS) persist for more than 10 years in the majority of patents, new data show. The study reports on 210 Italian patients who underwent AHSCT between 2007 and 2019. Among the entire study cohort, 79.5% of patients had not experienced worsening of disability at 5 years, and 65.5% had not experienced it at 10 years.

Patients with relapsing remitting MS had better results, with 85.5% experiencing no worsening of disability at 5 years, and 71.3% at 10 years. Among patients with progressive MS, 71.0% showed no worsening of disability at 5 years, and 57.2% at 10 years.

“This is the longest follow-up of AHSCT in MS patients so far to be reported,” said study author Matilde Inglese, MD, University of Genoa (Italy). “We have shown AHSCT to be highly effective to prevent long-term disability worsening in most treated patients.”

The study was published online Jan. 20 in Neurology.

“We suggest that AHSCT should be considered as a treatment strategy for MS not responding to conventional therapy,” the authors concluded.

The study had no control group, so a direct comparison is not possible. Nevertheless, Dr. Inglese said she believed these results are better than those that would be achieved with disease-modifying drug therapy for similar patients.

“The best patient candidates for this procedure are those with highly active multiple sclerosis who are not responsive to high-efficacy drugs, such as alemtuzumab or ocrelizumab,” Dr. Inglese commented. “Younger patients with an aggressive form of relapsing remitting MS tend to do the best, although patients with progressive forms of MS who still have active lesions on MRI also benefit.”
 

Renewing the immune system

The transplant procedure involves giving high-dose cyclophosphamide to stimulate mobilization of bone marrow stem cells, which are collected from peripheral blood. Patients then undergo intense immunosuppression with a cocktail of drugs to remove the autoreactive T cells, and the stem cells, which are not autoreactive, are reinfused.

“We are effectively renewing the immune system,” Dr. Inglese said. “While it is not correct to call it a cure, as we are not eliminating the etiology of the disease, it is the closest to complete suppression of the disease that we can get.”

Other results from the study show that among patients with relapsing remitting MS, rates of relapse-free survival were 78.1% at 5 years and 63.5% at 10 years.

Better results were achieved for patients who received the BEAM+ATG conditioning regimen for immunosuppression. That regimen includes carmustine, cytosine-arabinoside, etoposide, and melphalan, followed by rabbit antithymocyte globulin. Among patients with relapsing remitting disease who were treated with this protocol, rates of relapse-free survival were 86.4% at 5 years and 77.0% at 10 years.

For patients with relapsing remitting MS, the probability of achieving NEDA-3 status (no evidence of disease activity, including the absence of clinical relapses, disability worsening, and MRI inflammatory activity) was 62.2% at 5 years and 40.5% at 10 years.

Among those patients with relapsing remitting MS who received the BEAM+ATG conditioning protocol, NEDA-3 status was achieved in 67.7% at 5 years and in 54.9% at 10 years.

Three deaths occurred within 100 days following AHSCT (1.4% of the entire study population). One patient developed pulmonary thromboembolism, received fibrinolytic treatment, and died 48 hours later after intracranial hemorrhage. The second patient experienced engraftment failure and died 24 days after transplant because of an opportunistic infection. The third patient died 1 month after transplant from Wernicke-like encephalopathy. All the patients who died received the BEAM+ATG conditioning regimen. No transplant-related deaths occurred in patients who underwent transplant after 2007.

Dr. Inglese noted that the mortality rate associated with AHSCT has been greatly reduced in recent years. “We are seeing a very low mortality rate – about 0.3% – thanks to improvements in the procedure and better patient selection. This seems acceptable, given that we are treating patients with very aggressive disease who have a high risk of becoming significantly disabled relatively early in life,” she commented.

However, it is vitally important that the procedure be conducted in a specialized center with a highly experienced multidisciplinary team, she stressed.

In the Neurology article, the authors concluded: “Although patients with RRMS [relapsing remitting MS] are those who benefit the most from transplant, AHSCT has been also shown to prevent disability worsening in a large proportion of patients with active progressive MS.

“The BEAM+ATG conditioning protocol, although associated with a higher transplant mortality rate, was associated with a more pronounced suppression of clinical relapses and MRI inflammatory activity, allowing complete disease control in a higher proportion of patients,” they wrote.
 

Potent and durable efficacy, with caveats

Commenting on these latest findings, Jeffrey A. Cohen, MD, of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic, said: “AHSCT appears to have potent and durable efficacy in MS but is associated with significant risk and cost.”

The patients who are most likely to benefit are young and have experienced the onset of disease relatively recently. They are still ambulatory with highly active MS and have experienced recent clinical relapses and/or MRI lesion activity, and such activity continues despite disease-modifying therapy, Dr. Cohen noted. He added that “AHSCT is a reasonable option for such patients who have essentially failed the available disease-modifying therapy options.”

He pointed out that the key question is where AHSCT belongs in the overall MS algorithm relative to other high-efficacy therapies. “We need to know whether it should be used more broadly rather than as a last resort.”

To address that question, several randomized trials comparing AHSCT with high-efficacy disease-modifying therapy are in progress, including the National Institutes of Health–sponsored BEAT-MS trial in the United States (for which Dr. Cohen is the lead investigator) and four European trials – NET-MS (for which Dr. Inglese is the lead investigator), STAR-MS, RAM-MS, and COAST-MS.

The current study was partially funded and supported by the Italian Multiple Sclerosis Foundation. Dr. Inglese disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The benefits of autologous hematopoietic stem cell transplant (AHSCT) for patients with multiple sclerosis (MS) persist for more than 10 years in the majority of patents, new data show. The study reports on 210 Italian patients who underwent AHSCT between 2007 and 2019. Among the entire study cohort, 79.5% of patients had not experienced worsening of disability at 5 years, and 65.5% had not experienced it at 10 years.

Patients with relapsing remitting MS had better results, with 85.5% experiencing no worsening of disability at 5 years, and 71.3% at 10 years. Among patients with progressive MS, 71.0% showed no worsening of disability at 5 years, and 57.2% at 10 years.

“This is the longest follow-up of AHSCT in MS patients so far to be reported,” said study author Matilde Inglese, MD, University of Genoa (Italy). “We have shown AHSCT to be highly effective to prevent long-term disability worsening in most treated patients.”

The study was published online Jan. 20 in Neurology.

“We suggest that AHSCT should be considered as a treatment strategy for MS not responding to conventional therapy,” the authors concluded.

The study had no control group, so a direct comparison is not possible. Nevertheless, Dr. Inglese said she believed these results are better than those that would be achieved with disease-modifying drug therapy for similar patients.

“The best patient candidates for this procedure are those with highly active multiple sclerosis who are not responsive to high-efficacy drugs, such as alemtuzumab or ocrelizumab,” Dr. Inglese commented. “Younger patients with an aggressive form of relapsing remitting MS tend to do the best, although patients with progressive forms of MS who still have active lesions on MRI also benefit.”
 

Renewing the immune system

The transplant procedure involves giving high-dose cyclophosphamide to stimulate mobilization of bone marrow stem cells, which are collected from peripheral blood. Patients then undergo intense immunosuppression with a cocktail of drugs to remove the autoreactive T cells, and the stem cells, which are not autoreactive, are reinfused.

“We are effectively renewing the immune system,” Dr. Inglese said. “While it is not correct to call it a cure, as we are not eliminating the etiology of the disease, it is the closest to complete suppression of the disease that we can get.”

Other results from the study show that among patients with relapsing remitting MS, rates of relapse-free survival were 78.1% at 5 years and 63.5% at 10 years.

Better results were achieved for patients who received the BEAM+ATG conditioning regimen for immunosuppression. That regimen includes carmustine, cytosine-arabinoside, etoposide, and melphalan, followed by rabbit antithymocyte globulin. Among patients with relapsing remitting disease who were treated with this protocol, rates of relapse-free survival were 86.4% at 5 years and 77.0% at 10 years.

For patients with relapsing remitting MS, the probability of achieving NEDA-3 status (no evidence of disease activity, including the absence of clinical relapses, disability worsening, and MRI inflammatory activity) was 62.2% at 5 years and 40.5% at 10 years.

Among those patients with relapsing remitting MS who received the BEAM+ATG conditioning protocol, NEDA-3 status was achieved in 67.7% at 5 years and in 54.9% at 10 years.

Three deaths occurred within 100 days following AHSCT (1.4% of the entire study population). One patient developed pulmonary thromboembolism, received fibrinolytic treatment, and died 48 hours later after intracranial hemorrhage. The second patient experienced engraftment failure and died 24 days after transplant because of an opportunistic infection. The third patient died 1 month after transplant from Wernicke-like encephalopathy. All the patients who died received the BEAM+ATG conditioning regimen. No transplant-related deaths occurred in patients who underwent transplant after 2007.

Dr. Inglese noted that the mortality rate associated with AHSCT has been greatly reduced in recent years. “We are seeing a very low mortality rate – about 0.3% – thanks to improvements in the procedure and better patient selection. This seems acceptable, given that we are treating patients with very aggressive disease who have a high risk of becoming significantly disabled relatively early in life,” she commented.

However, it is vitally important that the procedure be conducted in a specialized center with a highly experienced multidisciplinary team, she stressed.

In the Neurology article, the authors concluded: “Although patients with RRMS [relapsing remitting MS] are those who benefit the most from transplant, AHSCT has been also shown to prevent disability worsening in a large proportion of patients with active progressive MS.

“The BEAM+ATG conditioning protocol, although associated with a higher transplant mortality rate, was associated with a more pronounced suppression of clinical relapses and MRI inflammatory activity, allowing complete disease control in a higher proportion of patients,” they wrote.
 

Potent and durable efficacy, with caveats

Commenting on these latest findings, Jeffrey A. Cohen, MD, of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic, said: “AHSCT appears to have potent and durable efficacy in MS but is associated with significant risk and cost.”

The patients who are most likely to benefit are young and have experienced the onset of disease relatively recently. They are still ambulatory with highly active MS and have experienced recent clinical relapses and/or MRI lesion activity, and such activity continues despite disease-modifying therapy, Dr. Cohen noted. He added that “AHSCT is a reasonable option for such patients who have essentially failed the available disease-modifying therapy options.”

He pointed out that the key question is where AHSCT belongs in the overall MS algorithm relative to other high-efficacy therapies. “We need to know whether it should be used more broadly rather than as a last resort.”

To address that question, several randomized trials comparing AHSCT with high-efficacy disease-modifying therapy are in progress, including the National Institutes of Health–sponsored BEAT-MS trial in the United States (for which Dr. Cohen is the lead investigator) and four European trials – NET-MS (for which Dr. Inglese is the lead investigator), STAR-MS, RAM-MS, and COAST-MS.

The current study was partially funded and supported by the Italian Multiple Sclerosis Foundation. Dr. Inglese disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The benefits of autologous hematopoietic stem cell transplant (AHSCT) for patients with multiple sclerosis (MS) persist for more than 10 years in the majority of patents, new data show. The study reports on 210 Italian patients who underwent AHSCT between 2007 and 2019. Among the entire study cohort, 79.5% of patients had not experienced worsening of disability at 5 years, and 65.5% had not experienced it at 10 years.

Patients with relapsing remitting MS had better results, with 85.5% experiencing no worsening of disability at 5 years, and 71.3% at 10 years. Among patients with progressive MS, 71.0% showed no worsening of disability at 5 years, and 57.2% at 10 years.

“This is the longest follow-up of AHSCT in MS patients so far to be reported,” said study author Matilde Inglese, MD, University of Genoa (Italy). “We have shown AHSCT to be highly effective to prevent long-term disability worsening in most treated patients.”

The study was published online Jan. 20 in Neurology.

“We suggest that AHSCT should be considered as a treatment strategy for MS not responding to conventional therapy,” the authors concluded.

The study had no control group, so a direct comparison is not possible. Nevertheless, Dr. Inglese said she believed these results are better than those that would be achieved with disease-modifying drug therapy for similar patients.

“The best patient candidates for this procedure are those with highly active multiple sclerosis who are not responsive to high-efficacy drugs, such as alemtuzumab or ocrelizumab,” Dr. Inglese commented. “Younger patients with an aggressive form of relapsing remitting MS tend to do the best, although patients with progressive forms of MS who still have active lesions on MRI also benefit.”
 

Renewing the immune system

The transplant procedure involves giving high-dose cyclophosphamide to stimulate mobilization of bone marrow stem cells, which are collected from peripheral blood. Patients then undergo intense immunosuppression with a cocktail of drugs to remove the autoreactive T cells, and the stem cells, which are not autoreactive, are reinfused.

“We are effectively renewing the immune system,” Dr. Inglese said. “While it is not correct to call it a cure, as we are not eliminating the etiology of the disease, it is the closest to complete suppression of the disease that we can get.”

Other results from the study show that among patients with relapsing remitting MS, rates of relapse-free survival were 78.1% at 5 years and 63.5% at 10 years.

Better results were achieved for patients who received the BEAM+ATG conditioning regimen for immunosuppression. That regimen includes carmustine, cytosine-arabinoside, etoposide, and melphalan, followed by rabbit antithymocyte globulin. Among patients with relapsing remitting disease who were treated with this protocol, rates of relapse-free survival were 86.4% at 5 years and 77.0% at 10 years.

For patients with relapsing remitting MS, the probability of achieving NEDA-3 status (no evidence of disease activity, including the absence of clinical relapses, disability worsening, and MRI inflammatory activity) was 62.2% at 5 years and 40.5% at 10 years.

Among those patients with relapsing remitting MS who received the BEAM+ATG conditioning protocol, NEDA-3 status was achieved in 67.7% at 5 years and in 54.9% at 10 years.

Three deaths occurred within 100 days following AHSCT (1.4% of the entire study population). One patient developed pulmonary thromboembolism, received fibrinolytic treatment, and died 48 hours later after intracranial hemorrhage. The second patient experienced engraftment failure and died 24 days after transplant because of an opportunistic infection. The third patient died 1 month after transplant from Wernicke-like encephalopathy. All the patients who died received the BEAM+ATG conditioning regimen. No transplant-related deaths occurred in patients who underwent transplant after 2007.

Dr. Inglese noted that the mortality rate associated with AHSCT has been greatly reduced in recent years. “We are seeing a very low mortality rate – about 0.3% – thanks to improvements in the procedure and better patient selection. This seems acceptable, given that we are treating patients with very aggressive disease who have a high risk of becoming significantly disabled relatively early in life,” she commented.

However, it is vitally important that the procedure be conducted in a specialized center with a highly experienced multidisciplinary team, she stressed.

In the Neurology article, the authors concluded: “Although patients with RRMS [relapsing remitting MS] are those who benefit the most from transplant, AHSCT has been also shown to prevent disability worsening in a large proportion of patients with active progressive MS.

“The BEAM+ATG conditioning protocol, although associated with a higher transplant mortality rate, was associated with a more pronounced suppression of clinical relapses and MRI inflammatory activity, allowing complete disease control in a higher proportion of patients,” they wrote.
 

Potent and durable efficacy, with caveats

Commenting on these latest findings, Jeffrey A. Cohen, MD, of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic, said: “AHSCT appears to have potent and durable efficacy in MS but is associated with significant risk and cost.”

The patients who are most likely to benefit are young and have experienced the onset of disease relatively recently. They are still ambulatory with highly active MS and have experienced recent clinical relapses and/or MRI lesion activity, and such activity continues despite disease-modifying therapy, Dr. Cohen noted. He added that “AHSCT is a reasonable option for such patients who have essentially failed the available disease-modifying therapy options.”

He pointed out that the key question is where AHSCT belongs in the overall MS algorithm relative to other high-efficacy therapies. “We need to know whether it should be used more broadly rather than as a last resort.”

To address that question, several randomized trials comparing AHSCT with high-efficacy disease-modifying therapy are in progress, including the National Institutes of Health–sponsored BEAT-MS trial in the United States (for which Dr. Cohen is the lead investigator) and four European trials – NET-MS (for which Dr. Inglese is the lead investigator), STAR-MS, RAM-MS, and COAST-MS.

The current study was partially funded and supported by the Italian Multiple Sclerosis Foundation. Dr. Inglese disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients will soon be able to read the notes that physicians make during an episode of care, as well as information about diagnostic testing and imaging results, tests for STDs, fetal ultrasounds, and cancer biopsies. This open access is raising concerns among physicians.

As part of the 21st Century Cures Act, patients have the right to see their medical notes. Known as Open Notes, the policy will go into effect on April 5, 2021. The Department of Health & Human Services recently changed the original start date, which was to be Nov. 2, 2020.

The mandate has some physicians worrying about potential legal risks and possible violation of doctor-patient confidentiality. When asked to share their views on the new Open Notes mandate, many physicians expressed their concerns but also cited some of the positive effects that could come from this.
 

Potentially more legal woes for physicians?

A key concern raised by one physician commenter is that patients could misunderstand legitimate medical terminology or even put a physician in legal crosshairs. For example, a medical term such as “spontaneous abortion” could be misconstrued by patients. A physician might write notes with the idea that a patient is reading them and thus might alter those notes in a way that creates legal trouble.

“This layers another level of censorship and legal liability onto physicians, who in attempting to be [politically correct], may omit critical information or have to use euphemisms in order to avoid conflict,” one physician said.

She also questioned whether notes might now have to be run through legal counsel before being posted to avoid potential liability.

Another doctor questioned how physicians would be able to document patients suspected of faking injuries for pain medication, for example. Could such documentation lead to lawsuits for the doctor?

As one physician noted, some patients “are drug seekers. Some refuse to aid in their own care. Some are malingerers. Not documenting that is bad medicine.”

The possibility of violating doctor-patient confidentiality laws, particularly for teenagers, could be another negative effect of Open Notes, said one physician.

“Won’t this violate the statutes that teenagers have the right to confidential evaluations?” the commenter mused. “If charts are to be immediately available, then STDs and pregnancies they weren’t ready to talk about will now be suddenly known by their parents.”

One doctor has already faced this issue. “I already ran into this problem once,” he noted. “Now I warn those on their parents’ insurance before I start the visit. I have literally had a patient state, ‘well then we are done,’ and leave without being seen due to it.”

Another physician questioned the possibility of having to write notes differently than they do now, especially if the patients have lower reading comprehension abilities.

One physician who uses Open Notes said he receives patient requests for changes that have little to do with the actual diagnosis and relate to ancillary issues. He highlighted patients who “don’t want psych diagnosis in their chart or are concerned a diagnosis will raise their insurance premium, so they ask me to delete it.”
 

Will Open Notes erode patient communication?

One physician questioned whether it would lead to patients being less open and forthcoming about their medical concerns with doctors.

“The main problem I see is the patient not telling me the whole story, or worse, telling me the story, and then asking me not to document it (as many have done in the past) because they don’t want their spouse, family, etc. to read the notes and they have already given their permission for them to do so, for a variety of reasons,” he commented. “This includes topics of STDs, infidelity, depression, suicidal thoughts, and other symptoms the patient doesn’t want their family to read about.”
 

Some physicians envision positive developments

Many physicians are unconcerned by the new mandate. “I see some potential good in this, such as improving doctor-patient communication and more scrupulous charting,” one physician said.

A doctor working in the U.S. federal health care system noted that open access has been a part of that system for decades.

“Since health care providers work in this unveiled setting for their entire career, they usually know how to write appropriate clinical notes and what information needs to be included in them,” he wrote. “Now it’s time for the rest of the medical community to catch up to a reality that we have worked within for decades now.

“The world did not end, malpractice complaints did not increase, and physician/patient relationships were not damaged. Living in the information age, archaic practices like private notes were surely going to end at some point.”

One doctor who has been using Open Notes has had experiences in which the patient noted an error in the medical chart that needed correcting. “I have had one patient correct me on a timeline in the HPI which was helpful and I made the requested correction in that instance,” he said.

Another physician agreed. “I’ve had patients add or correct valuable information I’ve missed. Good probably outweighs the bad if we set limits on behaviors expressed by the personality disordered group. The majority of people don’t seem to care and still ask me ‘what would you do’ or ‘tell me what to do.’ It’s all about patient/physician trust.”

Another talked about how Open Notes should have little or no impact. “Here’s a novel concept – talking to our patients,” he commented. “There is nothing in every one of my chart notes that has not already been discussed with my patients and I dictate (speech to text) my findings and plan in front of them. So, if they are reviewing my office notes, it will only serve to reinforce what we have already discussed.”

“I don’t intend to change anything,” he added. “Chances are if they were to see a test result before I have a chance to discuss it with them, they will have already ‘Googled’ its meaning and we can have more meaningful interaction if they have a basic understanding of the test.”

“I understand that this is anxiety provoking, but in general I think it is appropriate for patients to have access to their notes,” said another physician. “If physicians write lousy notes that say they did things they didn’t do, that fail to actually state a diagnosis and a plan (and they often do), that is the doc’s problem, not the patient’s.”

A version of this article first appeared on Medscape.com.

Patients will soon be able to read the notes that physicians make during an episode of care, as well as information about diagnostic testing and imaging results, tests for STDs, fetal ultrasounds, and cancer biopsies. This open access is raising concerns among physicians.

As part of the 21st Century Cures Act, patients have the right to see their medical notes. Known as Open Notes, the policy will go into effect on April 5, 2021. The Department of Health & Human Services recently changed the original start date, which was to be Nov. 2, 2020.

The mandate has some physicians worrying about potential legal risks and possible violation of doctor-patient confidentiality. When asked to share their views on the new Open Notes mandate, many physicians expressed their concerns but also cited some of the positive effects that could come from this.
 

Potentially more legal woes for physicians?

A key concern raised by one physician commenter is that patients could misunderstand legitimate medical terminology or even put a physician in legal crosshairs. For example, a medical term such as “spontaneous abortion” could be misconstrued by patients. A physician might write notes with the idea that a patient is reading them and thus might alter those notes in a way that creates legal trouble.

“This layers another level of censorship and legal liability onto physicians, who in attempting to be [politically correct], may omit critical information or have to use euphemisms in order to avoid conflict,” one physician said.

She also questioned whether notes might now have to be run through legal counsel before being posted to avoid potential liability.

Another doctor questioned how physicians would be able to document patients suspected of faking injuries for pain medication, for example. Could such documentation lead to lawsuits for the doctor?

As one physician noted, some patients “are drug seekers. Some refuse to aid in their own care. Some are malingerers. Not documenting that is bad medicine.”

The possibility of violating doctor-patient confidentiality laws, particularly for teenagers, could be another negative effect of Open Notes, said one physician.

“Won’t this violate the statutes that teenagers have the right to confidential evaluations?” the commenter mused. “If charts are to be immediately available, then STDs and pregnancies they weren’t ready to talk about will now be suddenly known by their parents.”

One doctor has already faced this issue. “I already ran into this problem once,” he noted. “Now I warn those on their parents’ insurance before I start the visit. I have literally had a patient state, ‘well then we are done,’ and leave without being seen due to it.”

Another physician questioned the possibility of having to write notes differently than they do now, especially if the patients have lower reading comprehension abilities.

One physician who uses Open Notes said he receives patient requests for changes that have little to do with the actual diagnosis and relate to ancillary issues. He highlighted patients who “don’t want psych diagnosis in their chart or are concerned a diagnosis will raise their insurance premium, so they ask me to delete it.”
 

Will Open Notes erode patient communication?

One physician questioned whether it would lead to patients being less open and forthcoming about their medical concerns with doctors.

“The main problem I see is the patient not telling me the whole story, or worse, telling me the story, and then asking me not to document it (as many have done in the past) because they don’t want their spouse, family, etc. to read the notes and they have already given their permission for them to do so, for a variety of reasons,” he commented. “This includes topics of STDs, infidelity, depression, suicidal thoughts, and other symptoms the patient doesn’t want their family to read about.”
 

Some physicians envision positive developments

Many physicians are unconcerned by the new mandate. “I see some potential good in this, such as improving doctor-patient communication and more scrupulous charting,” one physician said.

A doctor working in the U.S. federal health care system noted that open access has been a part of that system for decades.

“Since health care providers work in this unveiled setting for their entire career, they usually know how to write appropriate clinical notes and what information needs to be included in them,” he wrote. “Now it’s time for the rest of the medical community to catch up to a reality that we have worked within for decades now.

“The world did not end, malpractice complaints did not increase, and physician/patient relationships were not damaged. Living in the information age, archaic practices like private notes were surely going to end at some point.”

One doctor who has been using Open Notes has had experiences in which the patient noted an error in the medical chart that needed correcting. “I have had one patient correct me on a timeline in the HPI which was helpful and I made the requested correction in that instance,” he said.

Another physician agreed. “I’ve had patients add or correct valuable information I’ve missed. Good probably outweighs the bad if we set limits on behaviors expressed by the personality disordered group. The majority of people don’t seem to care and still ask me ‘what would you do’ or ‘tell me what to do.’ It’s all about patient/physician trust.”

Another talked about how Open Notes should have little or no impact. “Here’s a novel concept – talking to our patients,” he commented. “There is nothing in every one of my chart notes that has not already been discussed with my patients and I dictate (speech to text) my findings and plan in front of them. So, if they are reviewing my office notes, it will only serve to reinforce what we have already discussed.”

“I don’t intend to change anything,” he added. “Chances are if they were to see a test result before I have a chance to discuss it with them, they will have already ‘Googled’ its meaning and we can have more meaningful interaction if they have a basic understanding of the test.”

“I understand that this is anxiety provoking, but in general I think it is appropriate for patients to have access to their notes,” said another physician. “If physicians write lousy notes that say they did things they didn’t do, that fail to actually state a diagnosis and a plan (and they often do), that is the doc’s problem, not the patient’s.”

A version of this article first appeared on Medscape.com.

Patients will soon be able to read the notes that physicians make during an episode of care, as well as information about diagnostic testing and imaging results, tests for STDs, fetal ultrasounds, and cancer biopsies. This open access is raising concerns among physicians.

As part of the 21st Century Cures Act, patients have the right to see their medical notes. Known as Open Notes, the policy will go into effect on April 5, 2021. The Department of Health & Human Services recently changed the original start date, which was to be Nov. 2, 2020.

The mandate has some physicians worrying about potential legal risks and possible violation of doctor-patient confidentiality. When asked to share their views on the new Open Notes mandate, many physicians expressed their concerns but also cited some of the positive effects that could come from this.
 

Potentially more legal woes for physicians?

A key concern raised by one physician commenter is that patients could misunderstand legitimate medical terminology or even put a physician in legal crosshairs. For example, a medical term such as “spontaneous abortion” could be misconstrued by patients. A physician might write notes with the idea that a patient is reading them and thus might alter those notes in a way that creates legal trouble.

“This layers another level of censorship and legal liability onto physicians, who in attempting to be [politically correct], may omit critical information or have to use euphemisms in order to avoid conflict,” one physician said.

She also questioned whether notes might now have to be run through legal counsel before being posted to avoid potential liability.

Another doctor questioned how physicians would be able to document patients suspected of faking injuries for pain medication, for example. Could such documentation lead to lawsuits for the doctor?

As one physician noted, some patients “are drug seekers. Some refuse to aid in their own care. Some are malingerers. Not documenting that is bad medicine.”

The possibility of violating doctor-patient confidentiality laws, particularly for teenagers, could be another negative effect of Open Notes, said one physician.

“Won’t this violate the statutes that teenagers have the right to confidential evaluations?” the commenter mused. “If charts are to be immediately available, then STDs and pregnancies they weren’t ready to talk about will now be suddenly known by their parents.”

One doctor has already faced this issue. “I already ran into this problem once,” he noted. “Now I warn those on their parents’ insurance before I start the visit. I have literally had a patient state, ‘well then we are done,’ and leave without being seen due to it.”

Another physician questioned the possibility of having to write notes differently than they do now, especially if the patients have lower reading comprehension abilities.

One physician who uses Open Notes said he receives patient requests for changes that have little to do with the actual diagnosis and relate to ancillary issues. He highlighted patients who “don’t want psych diagnosis in their chart or are concerned a diagnosis will raise their insurance premium, so they ask me to delete it.”
 

Will Open Notes erode patient communication?

One physician questioned whether it would lead to patients being less open and forthcoming about their medical concerns with doctors.

“The main problem I see is the patient not telling me the whole story, or worse, telling me the story, and then asking me not to document it (as many have done in the past) because they don’t want their spouse, family, etc. to read the notes and they have already given their permission for them to do so, for a variety of reasons,” he commented. “This includes topics of STDs, infidelity, depression, suicidal thoughts, and other symptoms the patient doesn’t want their family to read about.”
 

Some physicians envision positive developments

Many physicians are unconcerned by the new mandate. “I see some potential good in this, such as improving doctor-patient communication and more scrupulous charting,” one physician said.

A doctor working in the U.S. federal health care system noted that open access has been a part of that system for decades.

“Since health care providers work in this unveiled setting for their entire career, they usually know how to write appropriate clinical notes and what information needs to be included in them,” he wrote. “Now it’s time for the rest of the medical community to catch up to a reality that we have worked within for decades now.

“The world did not end, malpractice complaints did not increase, and physician/patient relationships were not damaged. Living in the information age, archaic practices like private notes were surely going to end at some point.”

One doctor who has been using Open Notes has had experiences in which the patient noted an error in the medical chart that needed correcting. “I have had one patient correct me on a timeline in the HPI which was helpful and I made the requested correction in that instance,” he said.

Another physician agreed. “I’ve had patients add or correct valuable information I’ve missed. Good probably outweighs the bad if we set limits on behaviors expressed by the personality disordered group. The majority of people don’t seem to care and still ask me ‘what would you do’ or ‘tell me what to do.’ It’s all about patient/physician trust.”

Another talked about how Open Notes should have little or no impact. “Here’s a novel concept – talking to our patients,” he commented. “There is nothing in every one of my chart notes that has not already been discussed with my patients and I dictate (speech to text) my findings and plan in front of them. So, if they are reviewing my office notes, it will only serve to reinforce what we have already discussed.”

“I don’t intend to change anything,” he added. “Chances are if they were to see a test result before I have a chance to discuss it with them, they will have already ‘Googled’ its meaning and we can have more meaningful interaction if they have a basic understanding of the test.”

“I understand that this is anxiety provoking, but in general I think it is appropriate for patients to have access to their notes,” said another physician. “If physicians write lousy notes that say they did things they didn’t do, that fail to actually state a diagnosis and a plan (and they often do), that is the doc’s problem, not the patient’s.”

A version of this article first appeared on Medscape.com.

The role of imaging in diagnosing progressive multiple sclerosis (MS) and in assessing prognosis is the subject of a new review.

MRI is central in the diagnostic work-up of patients suspected of having MS, given its high sensitivity in detecting disease dissemination in space and over time and its notable ability to exclude mimics of MS, the authors noted. However, diagnosis of primary progressive MS remains challenging and is only possible retrospectively on the basis of clinical assessment.

Identification of imaging features associated with primary progressive MS and features that predict evolution from relapsing remitting MS to secondary progressive MS is an important, unmet need, they wrote.

Diagnosis of progressive MS is limited by difficulties in distinguishing accumulating disability caused by inflammatory disease activity from that attributable to degenerative processes associated with secondary progressive MS. Moreover, there are no accepted clinical criteria for diagnosing secondary progressive MS, the authors explained.

This need has promoted extensive research in the field of imaging, facilitated by definition of novel MRI sequences, to identify imaging features reflecting pathophysiological mechanisms relevant to the pathobiology of progressive MS, the authors said.

The current review reports the conclusions of a workshop held in Milan in November 2019, at which an expert panel of neurologists and neuroradiologists addressed the role of MRI in progressive MS.

Massimo Filippi, MD, IRCCS San Raffaele Scientific Institute, Milan, was the lead author of the review, which was published online Dec. 14, 2020, in JAMA Neurology.

The authors concluded that no definitive, qualitative clinical, immunologic, histopathologic, or neuroimaging features differentiate primary progressive and secondary progressive forms of MS; both are characterized by neurodegenerative phenomena and a gradual and irreversible accumulation of clinical disability, which is also affected by aging and comorbidities.

A definitive diagnosis of primary progressive MS is more difficult than a diagnosis of relapsing remitting MS; in part, primary progressive MS is a diagnosis of exclusion because it can be mimicked by other conditions clinically and radiologically, the authors noted.

The writers did report that, although nonspecific, some spinal cord imaging features are typical of primary progressive MS. These include diffuse abnormalities and lesions involving gray matter and two or more white-matter columns, but confirmation of this is required.

In patients with primary progressive MS and those with relapse-onset MS, MRI features at disease onset predict long-term disability and a progressive disease course. These features include lesions in critical central nervous system regions (i.e., spinal cord, infratentorial regions, and gray matter) and high inflammatory activity in the first years after disease onset. These measures are evaluable in clinical practice, the authors said.

In patients with established MS, gray-matter involvement and neurodegeneration are associated with accelerated clinical worsening; however, detection validation and standardization need to be implemented at the individual patient level, they commented.

Novel candidate imaging biomarkers, such as subpial demyelination, and the presence of slowly expanding lesions or paramagnetic rim lesions may identify progressive MS but should be further investigated, they added.

Discovery of MRI markers capable of detecting evolution from relapsing-remitting to secondary progressive MS remains an unmet need that will probably require multiparametric MRI studies, because it is unlikely that a single MRI method will be able to allow clinicians to optimally distinguish among these stages, the authors said.

The contribution of these promising MRI measures combined with other biomarkers, such as quantification of serum neurofilament light chain levels or optical coherence tomography assessment, should be explored to improve the identification of patients with progressive MS, they concluded.
 

‘A comprehensive review’

In a comment, Jeffrey A. Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, said the article is a comprehensive review of the pathologic mechanisms that underlie progression in MS and the proxy measures of those processes (brain and spinal cord MRI, PET, optical coherence tomography, and biomarkers).

“The paper reports there is no qualitative difference between relapsing remitting and progressive MS; rather, the difference is quantitative,” Dr. Cohen noted. “In other words, the processes that underlie progression are present from the earliest stages of MS, becoming more prominent over time.”

The apparent transition to progressive MS, he added, “rather than representing a ‘transition,’ instead results from the accumulation of pathology over time, a shift from focal lesions to diffuse inflammation and damage, and unmasking of the damage due to decreased resiliency due to aging and failure of compensatory mechanisms (neuroplasticity and remyelination).”

Also commenting, Edward Fox, MD, director, MS Clinic of Central Texas and clinical associate professor, University of Texas, Austin, explained that loss of tissue is the main driver of progressive MS.

“We all look at imaging to confirm that the progressive symptoms expressed by the patient are related to demyelinating disease,” he said. “When I see MRI of the spinal cord showing multifocal lesions, especially if localized atrophy is seen in a region of the cord, I expect to hear a history of progressive deficits in gait and other signs of disability.”

Dr. Fox noted that, on MRI of the brain, gray matter atrophy both cortically and in the deep gray structures usually manifests as cognitive slowing and poorer performance in work and social situations.

“We hope that other biomarkers, such as neurofilament light chain, will add to this body of knowledge and give us a better grasp of the definition of neurodegeneration to confirm the clinical and radiographic findings,” he added.

Dr. Filippi has received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi, Genzyme, Takeda, and Teva Pharmaceutical Industries; and research support from ARiSLA, Biogen Idec, Fondazione Italiana Sclerosi Multipla, Italian Ministry of Health, Merck Serono, Novartis, Roche, and Teva.

A version of this article first appeared on Medscape.com.

The role of imaging in diagnosing progressive multiple sclerosis (MS) and in assessing prognosis is the subject of a new review.

MRI is central in the diagnostic work-up of patients suspected of having MS, given its high sensitivity in detecting disease dissemination in space and over time and its notable ability to exclude mimics of MS, the authors noted. However, diagnosis of primary progressive MS remains challenging and is only possible retrospectively on the basis of clinical assessment.

Identification of imaging features associated with primary progressive MS and features that predict evolution from relapsing remitting MS to secondary progressive MS is an important, unmet need, they wrote.

Diagnosis of progressive MS is limited by difficulties in distinguishing accumulating disability caused by inflammatory disease activity from that attributable to degenerative processes associated with secondary progressive MS. Moreover, there are no accepted clinical criteria for diagnosing secondary progressive MS, the authors explained.

This need has promoted extensive research in the field of imaging, facilitated by definition of novel MRI sequences, to identify imaging features reflecting pathophysiological mechanisms relevant to the pathobiology of progressive MS, the authors said.

The current review reports the conclusions of a workshop held in Milan in November 2019, at which an expert panel of neurologists and neuroradiologists addressed the role of MRI in progressive MS.

Massimo Filippi, MD, IRCCS San Raffaele Scientific Institute, Milan, was the lead author of the review, which was published online Dec. 14, 2020, in JAMA Neurology.

The authors concluded that no definitive, qualitative clinical, immunologic, histopathologic, or neuroimaging features differentiate primary progressive and secondary progressive forms of MS; both are characterized by neurodegenerative phenomena and a gradual and irreversible accumulation of clinical disability, which is also affected by aging and comorbidities.

A definitive diagnosis of primary progressive MS is more difficult than a diagnosis of relapsing remitting MS; in part, primary progressive MS is a diagnosis of exclusion because it can be mimicked by other conditions clinically and radiologically, the authors noted.

The writers did report that, although nonspecific, some spinal cord imaging features are typical of primary progressive MS. These include diffuse abnormalities and lesions involving gray matter and two or more white-matter columns, but confirmation of this is required.

In patients with primary progressive MS and those with relapse-onset MS, MRI features at disease onset predict long-term disability and a progressive disease course. These features include lesions in critical central nervous system regions (i.e., spinal cord, infratentorial regions, and gray matter) and high inflammatory activity in the first years after disease onset. These measures are evaluable in clinical practice, the authors said.

In patients with established MS, gray-matter involvement and neurodegeneration are associated with accelerated clinical worsening; however, detection validation and standardization need to be implemented at the individual patient level, they commented.

Novel candidate imaging biomarkers, such as subpial demyelination, and the presence of slowly expanding lesions or paramagnetic rim lesions may identify progressive MS but should be further investigated, they added.

Discovery of MRI markers capable of detecting evolution from relapsing-remitting to secondary progressive MS remains an unmet need that will probably require multiparametric MRI studies, because it is unlikely that a single MRI method will be able to allow clinicians to optimally distinguish among these stages, the authors said.

The contribution of these promising MRI measures combined with other biomarkers, such as quantification of serum neurofilament light chain levels or optical coherence tomography assessment, should be explored to improve the identification of patients with progressive MS, they concluded.
 

‘A comprehensive review’

In a comment, Jeffrey A. Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, said the article is a comprehensive review of the pathologic mechanisms that underlie progression in MS and the proxy measures of those processes (brain and spinal cord MRI, PET, optical coherence tomography, and biomarkers).

“The paper reports there is no qualitative difference between relapsing remitting and progressive MS; rather, the difference is quantitative,” Dr. Cohen noted. “In other words, the processes that underlie progression are present from the earliest stages of MS, becoming more prominent over time.”

The apparent transition to progressive MS, he added, “rather than representing a ‘transition,’ instead results from the accumulation of pathology over time, a shift from focal lesions to diffuse inflammation and damage, and unmasking of the damage due to decreased resiliency due to aging and failure of compensatory mechanisms (neuroplasticity and remyelination).”

Also commenting, Edward Fox, MD, director, MS Clinic of Central Texas and clinical associate professor, University of Texas, Austin, explained that loss of tissue is the main driver of progressive MS.

“We all look at imaging to confirm that the progressive symptoms expressed by the patient are related to demyelinating disease,” he said. “When I see MRI of the spinal cord showing multifocal lesions, especially if localized atrophy is seen in a region of the cord, I expect to hear a history of progressive deficits in gait and other signs of disability.”

Dr. Fox noted that, on MRI of the brain, gray matter atrophy both cortically and in the deep gray structures usually manifests as cognitive slowing and poorer performance in work and social situations.

“We hope that other biomarkers, such as neurofilament light chain, will add to this body of knowledge and give us a better grasp of the definition of neurodegeneration to confirm the clinical and radiographic findings,” he added.

Dr. Filippi has received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi, Genzyme, Takeda, and Teva Pharmaceutical Industries; and research support from ARiSLA, Biogen Idec, Fondazione Italiana Sclerosi Multipla, Italian Ministry of Health, Merck Serono, Novartis, Roche, and Teva.

A version of this article first appeared on Medscape.com.

The role of imaging in diagnosing progressive multiple sclerosis (MS) and in assessing prognosis is the subject of a new review.

MRI is central in the diagnostic work-up of patients suspected of having MS, given its high sensitivity in detecting disease dissemination in space and over time and its notable ability to exclude mimics of MS, the authors noted. However, diagnosis of primary progressive MS remains challenging and is only possible retrospectively on the basis of clinical assessment.

Identification of imaging features associated with primary progressive MS and features that predict evolution from relapsing remitting MS to secondary progressive MS is an important, unmet need, they wrote.

Diagnosis of progressive MS is limited by difficulties in distinguishing accumulating disability caused by inflammatory disease activity from that attributable to degenerative processes associated with secondary progressive MS. Moreover, there are no accepted clinical criteria for diagnosing secondary progressive MS, the authors explained.

This need has promoted extensive research in the field of imaging, facilitated by definition of novel MRI sequences, to identify imaging features reflecting pathophysiological mechanisms relevant to the pathobiology of progressive MS, the authors said.

The current review reports the conclusions of a workshop held in Milan in November 2019, at which an expert panel of neurologists and neuroradiologists addressed the role of MRI in progressive MS.

Massimo Filippi, MD, IRCCS San Raffaele Scientific Institute, Milan, was the lead author of the review, which was published online Dec. 14, 2020, in JAMA Neurology.

The authors concluded that no definitive, qualitative clinical, immunologic, histopathologic, or neuroimaging features differentiate primary progressive and secondary progressive forms of MS; both are characterized by neurodegenerative phenomena and a gradual and irreversible accumulation of clinical disability, which is also affected by aging and comorbidities.

A definitive diagnosis of primary progressive MS is more difficult than a diagnosis of relapsing remitting MS; in part, primary progressive MS is a diagnosis of exclusion because it can be mimicked by other conditions clinically and radiologically, the authors noted.

The writers did report that, although nonspecific, some spinal cord imaging features are typical of primary progressive MS. These include diffuse abnormalities and lesions involving gray matter and two or more white-matter columns, but confirmation of this is required.

In patients with primary progressive MS and those with relapse-onset MS, MRI features at disease onset predict long-term disability and a progressive disease course. These features include lesions in critical central nervous system regions (i.e., spinal cord, infratentorial regions, and gray matter) and high inflammatory activity in the first years after disease onset. These measures are evaluable in clinical practice, the authors said.

In patients with established MS, gray-matter involvement and neurodegeneration are associated with accelerated clinical worsening; however, detection validation and standardization need to be implemented at the individual patient level, they commented.

Novel candidate imaging biomarkers, such as subpial demyelination, and the presence of slowly expanding lesions or paramagnetic rim lesions may identify progressive MS but should be further investigated, they added.

Discovery of MRI markers capable of detecting evolution from relapsing-remitting to secondary progressive MS remains an unmet need that will probably require multiparametric MRI studies, because it is unlikely that a single MRI method will be able to allow clinicians to optimally distinguish among these stages, the authors said.

The contribution of these promising MRI measures combined with other biomarkers, such as quantification of serum neurofilament light chain levels or optical coherence tomography assessment, should be explored to improve the identification of patients with progressive MS, they concluded.
 

‘A comprehensive review’

In a comment, Jeffrey A. Cohen, MD, director of the Cleveland Clinic’s Mellen Center for MS Treatment and Research, said the article is a comprehensive review of the pathologic mechanisms that underlie progression in MS and the proxy measures of those processes (brain and spinal cord MRI, PET, optical coherence tomography, and biomarkers).

“The paper reports there is no qualitative difference between relapsing remitting and progressive MS; rather, the difference is quantitative,” Dr. Cohen noted. “In other words, the processes that underlie progression are present from the earliest stages of MS, becoming more prominent over time.”

The apparent transition to progressive MS, he added, “rather than representing a ‘transition,’ instead results from the accumulation of pathology over time, a shift from focal lesions to diffuse inflammation and damage, and unmasking of the damage due to decreased resiliency due to aging and failure of compensatory mechanisms (neuroplasticity and remyelination).”

Also commenting, Edward Fox, MD, director, MS Clinic of Central Texas and clinical associate professor, University of Texas, Austin, explained that loss of tissue is the main driver of progressive MS.

“We all look at imaging to confirm that the progressive symptoms expressed by the patient are related to demyelinating disease,” he said. “When I see MRI of the spinal cord showing multifocal lesions, especially if localized atrophy is seen in a region of the cord, I expect to hear a history of progressive deficits in gait and other signs of disability.”

Dr. Fox noted that, on MRI of the brain, gray matter atrophy both cortically and in the deep gray structures usually manifests as cognitive slowing and poorer performance in work and social situations.

“We hope that other biomarkers, such as neurofilament light chain, will add to this body of knowledge and give us a better grasp of the definition of neurodegeneration to confirm the clinical and radiographic findings,” he added.

Dr. Filippi has received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi, Genzyme, Takeda, and Teva Pharmaceutical Industries; and research support from ARiSLA, Biogen Idec, Fondazione Italiana Sclerosi Multipla, Italian Ministry of Health, Merck Serono, Novartis, Roche, and Teva.

A version of this article first appeared on Medscape.com.

Key clinical point: The unified protocol (UP), a transdiagnostic skill-based therapy, is effective for the treatment of emotional disorders in multiple sclerosis (MS).

Major finding: Compared with treatment as usual (TAU), the UP intervention group significantly improved depression, anxiety, emotional dysregulation, positive and negative affects, and worry symptoms (P less than .001 for all).

Study details: Seventy adults with MS were randomly assigned to either UP or TAU group.

Disclosures: The authors received no financial support for the research, authorship, and/or publication of the study. The authors declared no conflicts of interest.

Source: Nazari N et al. BMC Psychol. 2020 Oct 31. doi: 10.1186/s40359-020-00480-8.

Key clinical point: The unified protocol (UP), a transdiagnostic skill-based therapy, is effective for the treatment of emotional disorders in multiple sclerosis (MS).

Major finding: Compared with treatment as usual (TAU), the UP intervention group significantly improved depression, anxiety, emotional dysregulation, positive and negative affects, and worry symptoms (P less than .001 for all).

Study details: Seventy adults with MS were randomly assigned to either UP or TAU group.

Disclosures: The authors received no financial support for the research, authorship, and/or publication of the study. The authors declared no conflicts of interest.

Source: Nazari N et al. BMC Psychol. 2020 Oct 31. doi: 10.1186/s40359-020-00480-8.

Key clinical point: The unified protocol (UP), a transdiagnostic skill-based therapy, is effective for the treatment of emotional disorders in multiple sclerosis (MS).

Major finding: Compared with treatment as usual (TAU), the UP intervention group significantly improved depression, anxiety, emotional dysregulation, positive and negative affects, and worry symptoms (P less than .001 for all).

Study details: Seventy adults with MS were randomly assigned to either UP or TAU group.

Disclosures: The authors received no financial support for the research, authorship, and/or publication of the study. The authors declared no conflicts of interest.

Source: Nazari N et al. BMC Psychol. 2020 Oct 31. doi: 10.1186/s40359-020-00480-8.

Key clinical point: One year of natalizumab treatment in relapsing-remitting multiple sclerosis (RRMS) improved absenteeism and work productivity loss.

Major finding: One year of natalizumab exposure showed an early improvement in absenteeism scores (mean change, −4.2; P = .0190) and the work productivity loss scores (mean change, −7.2; P = .0456).

Study details: The data come from the WANT observational study of 91 Italian patients with RRMS.

Disclosures: The WANT study was funded by Biogen. The authors reported relationships with various pharmaceutical companies.

Source: Capra R et al. Neurol Sci. 2020 Nov 17. doi: 10.1007/s10072-020-04838-z.

Key clinical point: One year of natalizumab treatment in relapsing-remitting multiple sclerosis (RRMS) improved absenteeism and work productivity loss.

Major finding: One year of natalizumab exposure showed an early improvement in absenteeism scores (mean change, −4.2; P = .0190) and the work productivity loss scores (mean change, −7.2; P = .0456).

Study details: The data come from the WANT observational study of 91 Italian patients with RRMS.

Disclosures: The WANT study was funded by Biogen. The authors reported relationships with various pharmaceutical companies.

Source: Capra R et al. Neurol Sci. 2020 Nov 17. doi: 10.1007/s10072-020-04838-z.

Key clinical point: One year of natalizumab treatment in relapsing-remitting multiple sclerosis (RRMS) improved absenteeism and work productivity loss.

Major finding: One year of natalizumab exposure showed an early improvement in absenteeism scores (mean change, −4.2; P = .0190) and the work productivity loss scores (mean change, −7.2; P = .0456).

Study details: The data come from the WANT observational study of 91 Italian patients with RRMS.

Disclosures: The WANT study was funded by Biogen. The authors reported relationships with various pharmaceutical companies.

Source: Capra R et al. Neurol Sci. 2020 Nov 17. doi: 10.1007/s10072-020-04838-z.